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Septal lesions and emotionality in the rat Wexler, Norman 1970

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S E P T A L L E S I O N S AND E M O T I O N A L I T Y IN T H E RAT b y NORMAN WEXLER B . S c , M c G i l l U n i v e r s i t y , 1967 A t h e s i s s u b m i t t e d t o t h e F a c u l t y o f G r a d u a t e S t u d i e s , i n p a r t i a l f u l f i l l m e n t o f t h e d e g r e e o f M a s t e r o f A r t s i n t h e D e p a r t m e n t o f P s y c h o l o g y We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d THE U N I V E R S I T Y OF B R I T I S H C O L U M B I A S e p t e m b e r , 1970 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r a n a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l m a k e i t f r e e l y a v a i l a b l e f o r r e f e r e n c e a n d s t u d y . I f u r t h e r a g r e e t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e H e a d o f my D e p a r t m e n t o r by h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . D e p a r t m e n t o f P g y r h n l n g y The U n i v e r s i t y o f B r i t i s h C o l u m b i a V a n c o u v e r 8, C a n a d a Date S e p t e m b e r 3D , 197.0 ACKNOWLEDGEMENTS Thanks to Dr. Rod Wong and Dr. D.J. Albert for bearing with this thesis. John Jamieson rendered s t a t i s t i c a l advice and the University of B r i t i s h Columbia Health Service kindly provided laboratory f a c i l i t i e s . i i ABSTRACT The effects of septal lesions i n rats on the hyperglycaemic response to s t r e s s , adrenal weight and water intake were investigated. Tested four times post-operatively at approximately weekly i n t e r v a l s , septal rats did not manifest s i g n i f i c a n t l y d i f f e r e n t resting blood glucose levels than control animals nor did they demonstrate an abnormal degree of hyper-glycaemia following periods of unavoidable foot shock. No adrenal hypertrophy was evident i n septal subjects compared to controls. Daily water intake was s i g n i f i c a n t l y higher among septals. The results concerning blood sugar levels and adrenal weights are taken as evidence that septal rage may not represent true hyperemotionality since certain appropriate physiological concomitants are absent. A second experiment investigated resistance to capture and handling and aspects of open f i e l d behaviour i n septal and control rats following injections of chlorpromazine hydrochloride or sa l i n e . Septalectomized rats resisted handling and capture to a greater extent than controls, traversed fewer squares and demonstrated less rears i n an open f i e l d , and had a greater tendency to leave a home cage and enter an open f i e l d . Chlor-promazine affected neither control nor septal subjects except to suppress the tendency of septal rats to leave a home cage and enter an open f i e l d . The behaviour of septal rats i s discussed i n terms of apparent emotionality. i i i TABLE OF CONTENTS Acknowledgements i i Abstract — ; • i l l Introduction • 1 Experiment I 6 Subjects 6 Surgery and Histology — 6 Apparatus 7 Procedure 7 Results 9 Experiment II 1 5 Introduction :— 1 5 Subjects 1 7 Surgery and Histology •— 1 7 Apparatus • 1 7 Results 1 9 Discussion and Conclusions 32 Bibliography • 38 Appendix A • 4-3 i v INTRODUCTION The past fifteen years have seen a large number of studies concerning the effects of septal forebrain damage. Some of these effects, known collectively as the septal syndrome are; (a) increased water intake (Blass and Hanson, 1970); (b) both positive and negative changes in general activity levels depending on the component behaviours measured, (Douglas and Raphaelson, 1966; Nielson, Mclver, and Boswell, 1965); (c) f a c i l i t a t i o n of a preoperatively learned conditioned two-way active avoidance response and of postoperative acquisition of such a response (Kenyon and Kriekhaus, 1965); (d) impairment in the acquisition of a 1-way active avoidance response (Vanderwolf, 1964); (e) a d e f i c i t in both preoperatively and postoperatively acquired passive avoidance responses (Kaada, Rasmussen, and Kevin, 1962); (f) increased motivation for sucrose or saccharin (Beatty and Schwartzbaum, 1968; Carey, 1967); (g) decreased efficiency on a schedule of differential reinforcement at low rates accompanied by an increased rate of responding on a fixed interval schedule (Ellen and Powell, 1962). Virtually a l l investigators have reported that septal ablation results i n an overt change in behaviour termed variously as hyperemotionality, septal rage, or h y p e r i r r i t a b i l i t y . First observed by Brady and Nauta (1953), i t consists of an exaggerated startle or fear response to previously neutral stimuli and often vicious attack behaviour i n response to normal handling. Generally, this aspect of the septal syndrome dissipates within a month i f the animals are not handled and are housed separately although the duration may be reduced to as l i t t l e as two weeks by handling or colony housing (Heller, Harvey and Moore 1962; Brady and Nauta, 1953). Lints, (1965) however, found that septal lesions produced an increased sensitivity to electric shock at a time when the overt expression of i r r i t a b i l i t y had completely disappeared. This is taken to indicate that septal damage produces long term affective changes. Other investigators, however, have raised doubts concerning the role of the septal area i n the control of emotionality. McCleary (1961) disputes the val i d i t y of the designation "hyper emotionality" proposed by King (1958), suggesting rather that the apparently affective changes observed following septal lesions are due to a loss of response inhibition. This view is - 2 -supported by Kaada; Rasmussen, and Kevin (1962) who cite as evidence the contrasting pattern of changes found in passive versus active shock avoidance behaviour. Kaada, (1960) had earlier reported electrophysiological data suggesting that the septal area is involved in the control of somatic responsiveness. Schwartzbaum, Kellicut and Thompson, (1964) have concluded that the septal region is important in the normal inhibition of non-reinforced operant responses. This inhibition is postulated "to operate directly upon the expression of highly integrated somatomotor acti v i t y . " Lending support to the septal hyperemotionality concept are the results of studies by King and Meyer, (1958) and Schwartzbaum and Gay, (1966). These investigators found that amygdaloid lesions appear to reverse the exaggerated startle response and vicious reaction to handling caused by septal lesions. However, no reversal or change was observed in the impairment of response inhibitions in a fixed interval reinforcement situation. Since lesions of the amygdaloid nuclei are known to result in an emotionality shift opposite in direction to that observed following septal ablation (Wood, 1958; Kar l i , 1956), these studies might be taken as evidence that the septal syndrome is not a unitary phenomenon and that "true" emotionality changes co-exist alongside other changes connected to response inhibition impairment. In fact, Carey, (1967) suggests that some of the effects of septal lesions are dependent on locus and there is evidence (Petsch, Stumpf and Gogolak, 1962; Donovick, 1968) of specific nucleus function. Generally the reports of wildness and viciousness involve large lesions and extensive damage to the lateral and medial septal nuclei but studies by Harrison and Lyon (1957) and Thomas, Moore, Harvey and Hunt, (1959) have failed to identify any precise points involved i n producing the "Emotionality" changes. The object of the present investigation was to determine whether or not septal lesions produce a true affective change i.e. hyperemotionality defined physiologically as well as behaviourally. The concept of septal hyperemotionality as employed by both i t s proponents and opponents is based almost exclusively on behavioural data. Unfortunately i t is well known that frequently employed indices of emotionality such as open f i e l d behaviour, defecation, latency to emerge from a home cage etc. have often failed to correlate (King, 1968). In a study designed to determine relation-- 3 -ships between such indices with septalectomized animals, Singh, (1966) concludes that "Emotionality i s not unidimensional and d i f f e r e n t indices used to assess emotionality i n rats do not measure the same thing." He found for example that whereas septal rats take longer to leave t h e i r home cages, i n d i c a t i n g t i m i d i t y , they are not f e a r f u l i n that they remain i n the open f i e l d for longer periods of time. While behavioural measurement of emotionality presents the above type of problem, physiological indices are t h e o r e t i c a l l y more r e l i a b l e . I f we define emotionality as the constellation of physiological events triggered by s t r e s s f u l stimulation, then we can specify with certainty what these changes w i l l be. The general pituitary-adrenal response to stress i s r e l a t i v e l y w e l l understood and predictable (Selye, 1950). I t would seem appropriate then, to examine the effect of septal lesions on some aspects of this response. Kasper, (1965) hypothesized that septal damage would raise the l e v e l of pituitary-adrenal function i n response to s t r e s s f u l stimulation. Her study, which involved stressing septal rats at 5-10 minute inte r v a l s d a i l y v i a a i r blasts for one post operative month, produced a number of contradictions, however. Heavy p i t u i t a r i e s and adrenals and a very high p i t u i t a r y ACTH content i n lesioned unstresses! animals suggested pituitary-adrenal hyperfunction, while heavy thymuses atad low blood cor-ticosterone levels i n stressed septal animals suggested hypo function under stress. Kasper suggests that these seeming inconsistences may be due to the effects of altered behaviour on the relevant p h y s i o l o g i c a l responses interacting, with the d i r e c t effects of neural damage. Measurement of di r e c t manifestations of the pitmriLtary-adrenal function as u t i l i z e d by the Kasper study i s l i m i t e d by the requirement that the animal be s a c r i f i c e d i n order to obtain the data. Consequently only one measurement per subject i s possible. With regard to s e p t a l damage, where the behavioural "hyperemotionality" attenuates with tiime i t would be p a r t i c u l a r l y valuable to be able to make repeated meas.ma?es of some physio-l o g i c a l index of emotionality. One index which lends i t s e l f w e l l to such a procedure i s the hyperglycaemic response to stress i.e-„ the rapid r i s e i n blood glucose concentration normally observed i n mammals minutes after a - 4 -s t r e s s f u l stimulus has been applied. Well documented (Selye, 1950), this index represents a response d i r e c t l y dependent on changes i n p i t u i t a r y -adrenal function and because only a small blood sample i s required for analysis, the procedure can be repeated i n d e f i n i t e l y . Although there i s normally great v a r i a t i o n i n the resting blood glucose levels of i n d i v i d u a l members of the same species, this source of error i s minimized by calculating a percentage increase due to stress for each animal rather than an absolute increase following i t . Experiment I then, involved determining the hyperglycaemic response of septal rats subjected to a period of unavoidable foot shock. Since the glucose l e v e l following stress r i s e s to a peak and then declines over time, the i n t e r v a l between onset of foot shock and blood sampling was chosen to provide the maximal post shock glucose concentration (Delay and Soulirac, 1944). The procedure was repeated four times over a s i x week post operative period, this being the period during which the overt behavioural i r r i t a b i l i t y i n unhandled animals generally disappears. Although ingestion of large quantities of water over a short time can s i g n i f i c e n t l y e f f e c t blood solute concentrations, the expected r e l a t i v e l y minor increase i n water intake of the septal animals was monitored as a precaution. If we take behavioural data concerning rage, attack and s t a r t l e to be a v a l i d i n d i c a t i o n of "hyperemotionality" i n septal r a t s , we would expect data concerning the hyperglycaemic response to stress to lead to s i m i l a r conclusions. Septal subjects should manifest exaggerated resting blood glucose levels and a p a r t i c u l a r l y enhanced glycaemic response to stress. We would also expect this phenomenon to taper off over time and normal glucose levels to return within approximately 5-6 weeks. I f , however, the behavioural modifications are due to a disruption of somatomotor i n h i b i t i o n processes rather than hyperemotionality, then no s i g n i f i c a n t alterations should be apparent since such disruption i s presumably not accompanied by altered pituitary-adrenal a c t i v i t y . Experiment I also allowed examination of the adrenal gland weights at the time of s a c r i f i c e . Kasper (1965) reports adrenal hypertrophy i n septal rats following one month of a f a i r l y severe stress schedule. Since the - 5 -duration of stress involved i n the present study i s i n s i g n i f i c a n t compared to the l a t t e r study, noting the presence or absence of adrenal weight gain would allow us to run a check on Kasper's r e s u l t . She reported that the adrenals of non stressed septal rats were not s i g n i f i c a n t l y heavier than those of non stressed controls implying that only septalectomy combined with stress can produce adrenal hypertrophy. Of course absence of hyper-trophy i n septal animals that have not been severely stressed would tend to detract from the hyperemotionality theory. Experiment I Subjects Eighteen experimentally naive, male albino rats of the Wistar s t r a i n served as subjects. These were obtained from the University of B r i t i s h Columbia Zoology Vivarium and weighed 180-219 gm. at the time of surgery. A l l S_s were i n d i v i d u a l l y housed i n stainless s t e e l wire cages (8 i n . x 10 i n . x 8 in.) under continuous i l l u m i n a t i o n , received food and water ad l i b . and . were handled only during surgery and subsequent testing. P r i o r to surgery the S_s were randomly divided into equal experimental and control groups. Surgery and Histology Surgery was performed under ether anesthesia with the Ss head held stationary i n a Krieg model 51200 stereotaxic instrument. Anesthesia was maintained throughout the s u r g i c a l procedure by placing an ether soaked s t r i p of s t e r i l e cotton over the S_s snout. B i l a t e r a l septal lesions were produced i n the experimental group by passing a 2ma. anodal current (d.c.) for 20 sec. through a stainless s t e e l electrode which was Insl-x coated except for the t i p . The cathode was attached to the Ss t a i l . The coordinates (deGroot, 1959) were: 1.9 mm. anterior to bregma, 0.8 mm. l a t e r a l to the midline and 4.3 mm. below the surface .of the cortex. In the case of the control S_s, the electrode was lowered i n the same manner but no current was passed. A n t i - b i o t i c sulfanilamide powder was applied to the wound which was then closed with three or four sutures. Immediately following surgery a l l jSs were injected with 0.1 ml of metrazol stimulant (pentylenetelrazol lOOmg/ml) in t r a - p e r i t o n e a l l y and 0.2 ml of C r y s t i c i l l i n ( p e n icillin-procaine suspension) intramuscularly. A l l S_s were allowed a recovery period of 7-9 days i n t h e i r home cages p r i o r to the testing schedule. At the conclusion of the experiment the Ss were s a c r i f i c e d and the adrenal glands and spleen immediately removed, cleaned of connective tissue and weighed. The brain was removed and placed i n a formalin-saline solution. P r i o r to histology the brains were transferred to a 10% ethyl alcohol solu-t i o n for a few days. They were then frozen with l i q u i d carbon dioxide and 40u sections cut and stained with thionin. The lesions were evaluated by microscopic examination and the non lesioned control sections examined for possible damage or i n f e c t i o n . - 7 -Apparatus A l l S_s were stressed i n a wooden compartment 10 i n . long x 6 i n . wide x 12 i n . high, matte black i n colour and having a transparent l u c i t e hinged cover. The f l o o r consisted of a grid of brass rods each ~ i n . i n diameter and spaced 1/2 i n . apart. A 250 a current was passed through the grid for 3 sec. periods at 10 sec. int e r v a l s v i a a shock, source b u i l t by the Psychology Dept. workshop. Delivery was timed by a Gerbrands model PT-2A 16 mm. tape timer. Procedure Each S_was tested four times, the f i r s t t r i a l occurring 8-9 days after surgery and subsequent t r i a l s at 16, 28 and 40 days after surgery. The Ss were deprived of food for 3 hours p r i o r to each t r i a l i n order to eliminate the effe c t of recent food intake on blood glucose l e v e l s . A t r i a l consisted of picking the S out of i t s home cage with a gloved hand and placing i t i n a small wooden res t r a i n i n g box, out of which only the t a i l could protrude. The t a i l was immersed i n hot water for approximately 30 s e c , removed and t r i e d with paper towelling. The d i s t a l portion of the t a i l was then amputated with a scal p e l at a point approximately .75 i n . from the t i p . The flow of blood was stimulated by stroking the t a i l from base to t i p between forefinger and thumb while exerting moderate pressure. Blood was collected i n a small s l i g h t l y concave glass container-out of which exactly 0.1 ml was micro-pipetted and transferred with washing to a test tube containing 3.8 ml. of an iso t o n i c solution of copper sulphate and sodium sulphate. The S_ was then transferred to the shock compartment and the shock schedule activated for 4 minutes. The S_ then remained i n the compartment for a further 5 minutes without receiving shock after which a second blood sample was taken and the S_ replaced i n i t ' s home cage. The second blood sampling involved merely removing the scab formed over the f i r s t cut. Blood glucose concentrations were determined by a modified version of the Asatoor and King (1954) alkali n e copper reduction method. To the mixture of blood and isotonic copper sulphate-sodium sulphate solution was added 0.1 ml. of 10% sodium tungstate. This was centrifuged for 10 minutes and 1 ml. of the supernatant removed and added to 1 ml. of alkalin e t a r t r a t e s olution. This was heated i n a b o i l i n g water bath for 10 minutes, cooled - 8 -and to i t added 3 ml. of phosphomolybdic solution and 3 ml. of water. The res u l t i n g solution was mixed and read a f t e r 5 minutes i n a model K l e t t colorimeter using a red f i l t e r . At the same time 1 ml. of a working standard of known glucose concentration and a blank using 1 ml. of is o t o n i c sulphate solution were put up i n the same way. Mg. of glucose per hundred ml. of blood was calculated as follows: e.g. Reading of unknown - reading of blank ^ ^ n n Reading of known standard - reading of blank where the known standard i s = 2.5 mg/100 ml. As w e l l as blood sampling, a record of da i l y water intake was kept for a l l Ss during the f i r s t 3 post-operative weeks. The Ss were s a c r i f i c e d approximately 1 month after the l a s t t r i a l i RESULTS - EXPERIMENT I Resting blood glucose The mean resting blood glucose concentrations of both septalec-tomized and control Ss over 4 t r i a l s plus the t o t a l mean for each group are summarized i n Table 1. A l l means f a l l within what i s considered to be the normal range for this measure i n the rat (60-125 mg. per 100 ml.). No s i g n i f i c a n t differences were found between the t o t a l means nor between i n d i v i d u a l groups between or within groups for any given t r i a l s . Septal Ss then do not manifest abnormally high or low resting levels of blood glucose. Change i n blood glucose following stress Corelated _t tests revealed that both septal and control groups registered s i g n i f i c a n t increases i n blood glucose i n response to stress on a l l t r i a l s . Table 2 l i s t s the mean absolute increases and th e i r s i g n i f i -cance l e v e l s . There was great v a r i a b i l i t y among the blood glucose responses to stress of i n d i v i d u a l S_s when expressed as percentage changes. Among the septalectomized animals this measure showed a range from an increase of 145% to a decrease of 17%; among the controls from an increase of 77% to a decrease of 24%. The t o t a l number of decreases observed was small however, amounting to f i v e out of seventy-two observations. In a l l p r o b a b i l i t y these paradoxical drops i n the glucose l e v e l do not represent true decreases to response to stress. I t i s known that i f an animal whose blood sugar i s elevated due to stress continues to be stressed, rapid glucose u t i l i z a t i o n w i l l soon result i n a drop to below the pre stress l e v e l . I t i s l i k e l y that on f i v e occasions this occurred i n the present study. Only two increases of over 100% were recorded. There was l i t t l e consistency on the part of i n d i v i d u a l subjects who demonstrated very high or negative changes. For example, one animal recorded a decrease of 17% on t r i a l 1 and an increase of 61% on t r i a l 3. On the other hand another subject recorded an increase of 77% on t r i a l one but an increase of merely 5% on t r i a l 3. This type of fl u c t u a t i o n occurred among both septals and controls. The mean percent changes i n blood glucose concentration over the 4 t r i a l s as w e l l as the t o t a l mean for each group are presented i n Table 3. - 10 -An analysis of variance on this data i s summarized i n Table 4. No s i g n i f i c a n t main effect due either to septalectomy or t r i a l s was found. However, there -was a s i g n i f i c a n t i n t e r a c t i o n between septalectomy and t r i a l s . In order to specify this i n t e r a c t i o n a further analysis of variance for simple effects was performed and i s summarized i n Table 5. I t was found that there were no s i g n i f i c a n t differences between septalectomized and control animals for any t r i a l . Nor were there s i g n i f i c a n t differences between t r i a l s within the septal or control groups. For example, T r i a l 1 (Septal-44.3%) does not d i f f e r from T r i a l 1 (Control-27.7%) or from T r i a l 4 (Septal-20.4%). By v i s u a l inspection, then, the in t e r a c t i o n between septalectomy and t r i a l s indicates that during the i n i t i a l t r i a l s the septal animals showed a higher degree of per cent glucose change than the controls although these differences are not s i g n i f i c a n t . This numerical difference a l l but disappears by T r i a l 4. The great V a r i a b i l i t y i n the data suggests that this s i g n i f i c a n t i n t e r --action may represent a Type I error. Adrenal weights and water intake Table 6 summarizes the mean adrenal weights at the conclusion of the experiment and the mean dai l y water intake during the study. Both measures are related to t o t a l body weight (determined at the time of s a c r i f i c e ) . As expected, the septalectomized animals drank s i g n i f i c a n t l y more than the control subjects (p .05). However, casual observation indicated that the septal animals did not ingest abnormally large amounts of water over short periods of time. As mentioned e a r l i e r , i t i s reasonably safe to assume that the blood glucose levels of the septalectomized group were not affected by higher water intake l e v e l s . No s i g n i f i c a n t difference between the adrenal gland weights of the septal and control animals was apparent. - 11 -Table 1 Mean resting blood glucose concentration,in mg. per 100 ml. T r i a l 1 Septal Control 63.9 63.1 T r i a l 2 81.4 89.4 T r i a l 3 98.0 102.1 T r i a l 4 85.2 91.3 Total 82.1 86.4 Table 2 Mean r i s e i n blood glucose concentration i n mg. per 100 ml. following e l e c t r i c shock Septal _t P_ Control _t T r i a l 1 18.5 2.368 .05 T r i a l 1 16.3 . 2.7084 -e .05 T r i a l 2 29.3 5.1974 <.01 T r i a l 2 21.4 3.3642 €.01 T r i a l 3 30.7 4.2831 4.02 T r i a l 3 14.8 3.0382 «".02 T r i a l 4 16.0 4.4236 <-.01 T r i a l 4 16.0 3.2916 €.02 Table 3 Mean % change i n blood glucose concentration following e l e c t r i c shock Septal Control T r i a l 1 44.3 27.7 T r i a l 2 39.8 25.0 T r i a l 3 36.0 15.1 T r i a l 4 20.4 18.7 Total 35.1 21.6 - 12 -Table 4 Analysis of variance (two way with r e p l i c a t i o n on one factor)  % change i n Blood glucose concentration Source df ss ms I 2. Between Gp. 17 24006.1 1411.7 Septalectomy(S) 1 3307.6 3307.6 2.56 Error between 16 20698.5 1293.7 Within Gp. .54 34003.5 629.7 Trials(T) 3 2864.6 954.8 1.91 T x S 3 7091.7 2363.9 4.72 t-01 Error within 48 24047.2 501,0 - 13-Table 5 Analysis of variance for simple effects % change i n blood glucose concentration Source df ss ms Between Gp. At t r i a l 1 At t r i a l 2 At t r i a l 3 At t r i a l 4 Within c e l l Within Gp. Between t r i a l s for septals Between t r i a l s for controls Septalectomy x t r i a l s T r i a l s x subjects within Gp. 1 1 1 1 64 34.4 27.4 54.6 0.3 20698.5 48 80.8 24.9 7091.7 26806.1 34.4 27.4 54.6 0.3 323.4 26.9 8.3 2363.9 558.5 - 14 -Table 6 Mean adrenal weights and mean dai l y water Intake corrected for  body weight. Adrenal Wt. Water intake mgm. per gm. ml. per gm. Septal ' 1.074 0.1707 * Control 0.812 0.1245 * * t=2.5054 df=15 p-^.05 (two t a i l e d test) Experiment I I Experiment I I digresses somewhat from a direct physiological approach to the septal syndrome but s t i l l deals with the nature of changes i n "emotional" behaviour due to septal damage. More pre c i s e l y , i t would seem of interest to manipulate some of the behavioural ratings of emotionality (mentioned e a r l i e r ) v i a some agent whose behavioural and physiological effects are r e l a t i v e l y w e l l known. Rather than concern ourselves with the presence or absence of a s t a t i s t i c a l c o r r e l a t i o n between such ratings we intend to focus attention on how i n d i v i d u a l indices are affected by t h i s agent. Open f i e l d behaviour, resistance to handling, latency to emerge from a home cage etc. would be observed under the influence of a drug known to influence such behaviour and thought to have some connection with the limbic system. Such a drug i s chlorpromazine hydrochloride. A depressant, i t diminishes spontaneous motor a c t i v i t y (Goodman and Gillam, 1957) but does not necessarily impair behaviour; e.g. where mobility i s desireable animals treated with chlor-promazine may perform better than controls (Blough, 1958). Bindra and Bacon, (1959) found that chlorpromazine decreased some components of general a c t i v i t y while leaving others unaffected. Conditioned avoidance responses are blocked by i t although the unconditioned response to the noxious stimulus remains unaffected (Cook and Weidley, 1957). Nelson and Franklin, (1967) found that chlorpromazine f a c i l i t a t e d fear e x t i n c t i o n while Schallek, Kuehn and Jew (1962) reported depressed viciousness i n septal rats upon administration of a variety of compounds s i m i l a r chemically to chlorpromazine. Killam and Killam, (1958) found that chlorpromazine may depress the arousal response of the limbic system that i s characterized by slow high voltage waves. I t may also slow spontaneous limbic a c t i v i t y (Schallek, 1962) and has an i n h i b i t o r y e f f e c t on septal s e l f stimulation i n doses that do not disorganize behaviour generally (Olds and Travis, (1960); Olds,,I960). In rats having septal area lesions there i s usually an increase i n low amplitude c o r t i c a l EEG a c t i v i t y and a degrease i n the number of d.c. s h i f t s which can be blocked by the administration of chlorpromazine (Pirch and Norton, 1967). C l i n i c a l l y phlorpromazine i s widely employed to reduce anxiety and has been found to reduce pain s e n s i t i v i t y (Nickols, 1960). K l e t z k i n , (1962) suggests that the therapeutic value of chlorpromazine i s due to i t s disruption - 16 -o f a b n o r mal n e u r a l p a t t e r n s i n t h e l i m b i c s y s t e m . E x p e r i m e n t I I t h e n i s d e s i g n e d t o r e p l i c a t e once a g a i n t h e e f f e c t s o f s e p t a l l e s i o n s on " e m o t i o n a l " b e h a v i o u r and t o i n v e s t i g a t e t h e e f f e c t s o f c h l o r p r o m a z i n e a d m i n i s t r a t i o n on s u c h b e h a v i o u r . METHOD Subjects The Ss were 16 experimentally naive male albino rats weighing 350-380 gm. at the time of surgery. Other than the fact that they were obtained from Simonsen Breeding Laboratories (Los Angeles) a l l d e t a i l s were as i n Experiment I. Surgery and Histology. Surgical and h i s t o l o g i c a l procedures were i d e n t i c a l to those employed i n Experiment I except that Nembutal (sodium pentobarbital) anesthesia (1.5 mg./ 100 gm.) was u t i l i z e d i n place of ether and that the adrenal glands were not examined. Apparatus The apparatus consisted of an open f i e l d with i n t e r n a l dimensions 4 x 4 x 1 f t . The f l o o r and walls were painted with white enamel and the f l o o r surface marked off into sixteen equal squares by black l i n e s , approximately 1/8 i n . i n width. A black, matte wooden box (6 x 10 x 12 in.) with a hinged top was attached to one side of the open f i e l d and was separated from i t by a 3 x 4 i n . black g u i l l o t i n e door. The entire apparatus was situated i n a small room having a matte black c e i l i n g and matte dark grey walls. Illumination was provided by a 15 watt bulb held i n a black paper cylinder suspended 5 f t . above the open f i e l d . Procedure: Each S_ was given two t r i a l s , one following administration of chlor-promazine, the other following administration of salin e . The f i r s t t r i a l occurred 10-12 days after surgery, the second 2 days following T r i a l 1. The order of testing was counter balanced so that h a l f of each group received chlorpromazine f i r s t and saline second and the other half s a l i n e f i r s t and chlorpromazine second. A t r i a l consisted of s l i d i n g S_s cage out of the colony rack, covering the open top and carrying i t into the test room where i t was l e f t undisturbed for 10 minutes i n a pos i t i o n that did not allow the S_ to see the apparatus. The S_was then picked up with a gloved hand and injected i n t r a p e r i t o n e a l l y with chlorpromazine (.2 mg/lOOgm i n 1.6 ml d i s t i l l e d water) or a l i k e amount of saline and replaced i n the cage for 20 minutes. At the end of this period the S_ was picked up and was rated on a 1-7 scale for - 18 -resistance to capture and on the same scale for resistance to handling following capture. Resistance was considered i n terms of locomotion, v o c a l i z a t i o n , b i t i n g , clawing and struggling. The S_ was held for not more than approximately 20 sec. and then placed into the home box which was closed completely for 2 minutes. The g u i l l o t i n e door was then removed and the number of times S_s head emerged from the box and the number of times S_ placed approximately ha l f i t s body including both forelegs over the threshold were observed during a 10 min. period. At the end of this session the g u i l l o t i n e door was replaced, S_ removed through the top of the home box and placed back i n i t s cage. Two minutes were allowed to elapse after which S_ was picked up and placed onto one corner of the open f i e l d , facing the corner. During the next 5 minutes S_ was observed from one side and the number of squares traversed, the number of hind leg rears and the number of fe c a l boluses dropped were noted. At the conclusion of this session S_ was replaced i n i t s cage and returned to the animal colony. Between t r i a l s , the open f i e l d was washed with a solution of water and vinegar i n order to eliminate scent t r a i l s . RESULTS Experiment I I Resistance to capture and handling Table 7 provides a summary of mean ratings of resistance to capture and handling on 1 - 14 scale. At the time of observation separate ratings for resistance to capture and resistance to handling were made on a 1 - 7 scale. However, since i t i s d i f f i c u l t to specify when capture becomes handling, i t seemed prudent to combine the capture and handling scales for each animal. "Resistance" i s a somewhat subjective term. Factors taken into consideration include as indicated e a r l i e r ; v o c a l i z a t i o n , urination and defecation, locomotion (escape), squirming, b i t i n g and scratching. A given animal may, for example, have manifested only squirming or vo c a l i z a t i o n and yet rate a high score on the basis of i n t e n s i t y . The table i s arranged so that i t i s evident how the order of administration of chlorpromazine and saline affected the group means. This form of tabulation i s u t i l i z e d for the other measures i n Experiment I I as w e l l . A L a t i n Square analysis of variance (Bruning and Kintz, 1967) was per-formed on this data (again this type of analysis i s u t i l i z e d throughout Experiment II) and i s summarized i n Table 8. Septalectomized subjects were found to r e s i s t capture and handling to a greater extent than control animals (p x .05). Chlorpromazine administration, however, had no effect on either group. Neither did an order effect appear, there being no s i g n i f i c a n t difference i n the degree of resistance on f i r s t and second t r i a l s i n either group. No s i g n i f i c a n t interactions occurred. Open f i e l d behaviour  Squares traversed The mean number of squares traversed i n an open f i e l d apparatus over 5 minutes are indicated i n Table 9 while Table 10 provides a summary of the analysis of variance on the data. Septalectomized Ss traversed far fewer squares than the operated controls and this difference was highly s i g n i f i c a n t (p i: .001). Within groups order effect was found as w e l l , i n d i c a t i n g that among both septal and control subjects the f i r s t t r i a l produced a higher score than the second t r i a l regardless of whether saline or chlorpromazine was - 20 -u t i l i z e d . Apparently, the i n i t i a l 5 minute exposure to the open f i e l d plus the 10 minute opportunity to observe the apparatus from the home box resul t i n a degree of habituation that affects the second.trial. The administration of chlorpromazine did not affect the scores of either group, however, a s i g n i f i c a n t between groups drug by order i n t e r a c t i o n did occur. This means that the difference between receiving chlorpromazine f i r s t and chlorpromazine second i s greater among the operated controls than among the septal subjects. Rears Aside from simple ambulation, rearing up on the handlegs i s i n the rat the only other d i s t i n c t motor pattern that we may observe as contributing to exploratory or general a c t i v i t y i n an open f i e l d . I t i s not surprising then that results with regard to the number of rears recorded should p a r a l l e l the "squares traversed" data. Tables 11 and 12 summarize the number of rears i n the open f i e l d 5 minute session and provide the results of the analysis of variance. I t was found that septalectomized Ss demonstrated fewer rears (p '<. .025) then the operated controls and that i n both these groups higher scores were recorded on the f i r s t t r i a l than on the second. Again no effect i s a ttributable to the administration of chlorpromazine and unlike the "squares traversed" scores no s i g n i f i c a n t interactions occurred. j Defecation Tables 13 and 14 summarize the mean number of boluses dropped during the 5 minute open f i e l d session and the mean number of times the S_'s head emerged from a home box opening on the open f i e l d , respectively. Analysis of variance revealed no s i g n i f i c a n t effects or interactions. Half e x i t s The mean number of times i n 10 minutes that the j>s performed a half e x i t by placing both forelegs over the threshold of the home box are l i s t e d i n Table 15. A l l the operated controls and a l l the septalectomized Ss that were run under the chlorpromazine treatment had zero scores. Only the septalectomized S_s run under the saline condition registered p o s i t i v e scores. I t would appear - 21 -t h e n t h a t s e p t a l r a t s have a t e n d e n c y t o l e a v e a home cage w h i c h i s n o t p r e s e n t i n n o r m a l a n i m a l s . C h l o r p r o m a z i n e s u p p r e s s e s t h i s t e n d e n c y . Of c o u r s e , t h e s m a l l number o f h a l f e x i t s a c t u a l l y r e c o r d e d makes t h i s k i n d o f c o n c l u s i o n h i g h l y s p e c u l a t i v e . The same r e s e r v a t i o n s h o u l d a l s o a p p l y t o t h e f a c t t h a t o f t h e s e p t a l a n i m a l s t h a t d i d r e g i s t e r p o s i t i v e s c o r e s , the ones t h a t r e c e i v e d t h e s a l i n e i n j e c t i o n on t r i a l 1 s c o r e d h i g h e r t h a n t h o s e . t h a t r e c e i v e d i t on t r i a l 2. - 22 -Table 7. Mean rating of resistance to capture and handling on a 1-14 scale CPZ -chlorpromazine hydrochloride SAL -isot o n i c saline Septals order of admin- CPZ SAL - i s t r a t i o n s i - s4 CPZ - SAL 9.5 5.8 s5 - s8 SAL - CPZ 9.5 12.0 s i - s8 9.5 8.9 Controls order of admin- CPZ SAL - i s t r a t i o n s9 - s l 2 CPZ - SAL 4.5 5.0 s l 3 - sl6 SAL - CPZ 6.3 7.0 s9 - sl6 5.4 6.0 - 23 Table 8 Analysis of variance (Latin Square)  Resistance to handling and capture Source df Between gp. 15 Septalectomy (S) 1 CPZ x Order (0) 1 CPZ x S 1 Error 12 Sum of  squares 98.0 50.0 3.15 224.7 Mean  squares 98.0 50.0 3.15 18.73 5.2 2.67 0.17 ^ .05 Within Gp. CPZ Order CPZ x S 0 x S Error 16 1 1 1 1 12 130.0 0 21.2 ' 3.15 18.0 87.7 0 21,2 3.15 18.0 7.31 0 2.9 0.43 '2.46 - 24 -Table 9 Mean number of squares crossed i i i an open f i e l d apparatus  during a f i v e min. period. CPZ - chlorpromazine hydrochloride SAL - isoto n i c saline Septals Order of administration CPZ SAL s i s5 s i s4 s8 s8 CPZ - SAL SAL - CPZ 12.5 4.5 8.0 0 5.8 2.9 Controls Order of adminis t r a t i o n CPZ SAL s9 -s l 3 s9 -sl 2 - sl6 sl6 CPZ - SAL SAL - CPZ 56.5 8.5 32.5 47.3 35.8 41.5 - 25 -Table 10 -Analysis of variance (Latin Square) NO. of squares crossed i n an open f i e l d apparatus during a 5 min. period. Source df Siim of Mean F P_ squares squares Between Gp. 15 16119.9 - -Septalectomy (S) 1 7969.5 7969.5 20.75 *.001 CPZ x Order (0) 1 1845.2 1845.2 4.8 «-.05 CPZ x S 1 1696.6 1696.6 4.42 Error 12 4608.6 384.1 -Within Gp. 16 4321.5 240.1 -CPZ 1 30.0 30.0 0.15 Order 1 1212.7 1212.7 6.07 <:.05 CPZ x S 1 399.0 399.0 1.99 0 x S 1 282.0 282.0 1.41 Error 12 2397.6 199.8 -- 26 -Table 11 Mean number of- rears i n an open f i e l d apparatus during a  5 min. period. CPZ - chlorpromazine hydrocholride SAL - isotonic saline Septals Order of CPZ SAL adminis t r a t i o n s i - s4 CPZ - SAL 5.3 0 s5 - s8 SAL - CPZ 5.5 5.8 s i - s8 5.4 2.9 Controls Order of CPZ SAL administration s9 - sl2 CPZ - SAL 21.0 11.0 s l 3 - sl6 SAL - CPZ 6.0 14.7 s9 - sl6 13.5 12.9 Table 12 ..' Analysis of Variance (Latin. Square)  No. of rears i n an open f i e l d apparatus during a 5 min. period. Source df Sum of Mean • p squares •squares Between Gp. 15 1422.7 -Septalectomy (S) : l 657.0 657.7 8.17 CPZ x Order (0) l 13.8 13.8 0.17 CPZ x S l 148.0 148.0 1.84 Error 12 965.2 80.4 -Within Gp. 16 634.5 - -CPZ 1 19.5 19.5 1.03 Order 1 294.0 294.0 15.6 CPZ x.S 1 7.1 7.1 0.38 0 x S 1 87.8 87.8 4.6 Error 12 226.1 18.8 — - 28 -Table 13 Mean number of boluses excreted i i i an open f i e l d apparatus  during a f i v e minute period. CPZ 2. chlorpromazine hydrochloride SAL - isotonic saline Septals Order of CPZ . SAL administration s i - s4 CPZ - SAL 1.25 0.5 s5 - s8 SAL - CPZ 0.5 1.0 s i - s8 0.88 0.75 Controls Order of CPZ SAL administration s9 - s l 2 CPZ - SAL 1.0 0.25. sl3 - sl6 SAL - CPZ 0.75 1.25 s9 - sl6 ' 0.88 0.75 29 -.Table 14 Mean number of head emergences from a home box during a  10 min. period. CPZ - chlorpromazine hydrochloride SAL - isotonic saline Septals Order of CPZ SAL administration • s i - s4 CPZ - SAL 1.5 3.5 s5 - s8 SAL - CPZ 2.5 9.8 s i - s8 2.0 5.7 Controls Order of CPZ SAL administration s9 - s l 2 CPZ - SAL 3.0 2.0 s l 3 - sl6 SAL - CPZ 2.0 2.0 s9 - s16 2.5 2.0 - 30 -Table 15 Mean number of times both forelegs were placed over the  threshold of a home box e x i t during a 10 miri. period. Septals Order of CPZ SAL administration s i - s4 CPZ - SAL 0 1.5 s5 - s8 SAL - CPZ 0 5.0 s i - s8 0 3.3 Controls Order of CPZ SAL adminis t r a t i o n s9 - s l 2 CPZ- - SAL 0 0 sl3 - sl6 SAL - CPZ 0 0 s9 - sl6 0 0 - 31 -Anatomical findings - Experiments I and I I Appendix I contains h i s t o l o g i c a l reconstructions (deGroot, 1959) of septal damage i n each lesioned subject. Four representative sections per brain are shown 6.2, 7.0, 7.8, and 8.6 mm. anterior to bregma respec-t i v e l y . Examination shows that a l l lesions caused extensive damage to the l a t e r a l and medial septal n u c l e i . Six of the lesions included some damage to the fornix. In certain cases there appeared to be viable s t r i p s of tissue between the l a t e r a l n u c l e i , however, these do not appear i n the reconstructions since they were l o s t i n the sectioning process. In general there was a high degree of s i m i l a r i t y i n the extent and shape of the lesions. The brains of Ss from the control group were sectioned and examined for signs of i n f e c t i o n or other damage, however, none were found. Discussion and Conclusions Assuming that a r i s e i n the concentration of blood glucose i s a v a l i d indicant of a change In a rat's emotional state, the absence of any changes i n either the resting glucose l e v e l or the hyperglycaemic response to stress following septal lesions may be construed as evidence that such damage does not lead to hyperemotionality. The extreme i r r i t a b i l i t y generally reported i n the wake of lesions of the septum and confirmed i n Experiment I I must be explained otherwise. Since the response i n h i b i t i o n theory of the septal syndrome i s currently the only alternative hypothesis, i t i s i n d i r e c t l y supported. In defence of the concept of septal hyperemotionality one might suggest that i t i s unreasonable to expect to observe exaggerated glucose levels i n septal animals. The release of additional glucose into the blood stream during s t r e s s f u l periods would serve no.real adaptive function over and above the normal hyperglycaemic response, since the s t r e s s f u l stimulation presented to the septal animal i s no more physic a l l y harmful nor d i f f i c u l t to escape than i t i s to a normal one. Likewise a supra normal resting glucose l e v e l i n an undisturbed septal animal would serve no p a r t i c u a l r purpose. Perhaps what should be investigated with regard to blood levels i n septalectomized subjects i s the i r degree of s e n s i t i v i t y to stimulation. Can the hyperglycaemic response be triggered by a lower l e v e l of s t r e s s f u l stim-u l a t i o n i n a septal animal than i n a normal one? In other words, instead of looking for an exaggerated hyperglycaemic response to severe stimulation we would look for a simple hyperglycaemic response to a stimulus which would under ordinary circumstances not warrant such a response. Should this s i t u a -t i o n prove to be the case, i t would f a l l conveniently into l i n e with basic behavioural observations. Exaggerated s t a r t l e and attack behaviour, for example, which would be expected i n response to intense stimulation such as a sudden loud noise or a direct attack by another animal i s e l i c i t e d by simply opening a cage of a septalectomized animal. The trouble with a threshold approach such as this i s that i t tends to be a restatement of the response i n h i b i t i o n hypothesis modified to include - 33 -physiological responses as w e l l as behavioural ones.. I t places the emphasis on the magnitude of the stimulus required to e l i c i t a given response rather than on the magnitude of the response to a given stimulus. When dealing with physiological indices of emotionality or response to stress, however, i t i s the magnitude of the index rather than i t s threshold which has most often been established as the c r i t i c a l factor (Selye, 1959; Levi, 1965). For example, lesions of the amygdaloid area r e s u l t i n increased aggressiveness (Wood 1958) or increased p l a c i d i t y (King, 1959) depending on the locus of the damage. Accompanying the former, Bovard and Gloor (1961) and Anand (1957) reported an increase i n the corticosterone response to immobilization stress whereas Mason and Nauta (1959) found that the l a t t e r l e s i o n resulted i n the v i r t u a l disappearance of the 17-hydroxy co r t i c o s t e r o i d response to avoidance t r a i n i n g . P o i r i e r , Cordeau, Lemire and Ayotte, (1956) found that b i l a t e r a l amygdaloid damage of the type producing p l a c i d i t y , are followed by a b o l i t i o n of the hyperglycaemic response to stress. E l e c t r i c a l stimulation i n this area causes an increase i n 17- hydroxy-corticosteroid production (Mason, 1958) i n monkeys , Where neural damage i s not involved, the same type of quantitative changes have been reported. Henderson (1967) for example, found that rats with high behavioural emotionality scores due to preweaning noxious stimulation also have high resting blood sugar l e v e l s . In general, reports of quantitative changes i n endocrine and metabolic a c t i v i t y associated with changes i n emotionality or the response to s t r e s s f u l stimulation are very numerous. I t i s reasonable to expect, then, that i f septal lesions were -indeed producing an increase i n emotionality, this s i t u a t i o n should manifest i t s e l f i n a quantitatively measurable physiological manner. As far as blood glucose levels or adrenal weights are concerned, this has not been the case i n Experiment I. Rasper's (1965) investigation does, i n fact, encompass such findings. However, conclusions drawn from the various measures that were u t i l i z e d i n that study, are contradictory. Certain indices of p i t u i t a r y adrenal a c t i v i t y indicated hyperfunction i n septal animals, others no change at a l l . At the same time i t appeared that septalectomy reduces responsiveness to stress - 34 -although there was s i g n i f i c a n t adrenal hypertrophy. This l a s t point d i r e c t l y contradicts the findings of the present experiment which revealed no increase i n adrenal weights. A very probable explanation,, however, i s the simple difference i n the. duration of stress between.the two studies. Experiment I, although u t i l i z i n g a f a i r l y severe form of stress, did not expose the subjects to i t for anywhere near the length of time used by Kasper. I t may be concluded that septalectomy i t s e l f does not lead.to gains i n adrenal weight. Kasper, i n fact, did not find a s i g n i f i c a n t gain i n adrenal weight among her non-stressed septal animals. This was confirmed as w e l l by Clody and Carlton (1968). • _ ' ' -Unfortunately, other inconsistencies within the Kasper experiments and between that study and the present one do not y i e l d to c l a r i f i c a t i o n e a s i l y . One p o s s i b i l i t y that bears consideration i s that the behavioural modifications following septal lesions produce endocrine changes not d i r e c t l y related to the accompanying neural damage. As w e l l , the Kasper study r e l i e d on single measures of cumulative effects following a long period of stress while the present investigation involved repeated measures of a di f f e r e n t short term e f f e c t . I t i s d i f f i c u l t to say which approach i s more v a l i d . Repeated measures of a temporary change such as the hyperglycaemic response seem to be j u s t i f i a b l e because of the transient nature of the behavioural septal syndrome. Perhaps a more dir e c t index of pituitary-adrenal function i s i n order. Monitoring the levels of urinary ketosteroids following septalectomy i s one p o s s i b i l i t y . Another might involve repeated measures of plasms corticosterones i n amounts of blood not required s a c r i f i c e of the subject. Experiment I I generally f a i l e d to shed new l i g h t on the nature of the septal syndrome. Administration of chlorpromazine affected neither septal nor operated control animals with respect to resistance to capture and handling, open f i e l d behaviour or defecation. Only i n the case of h a l f - e x i t s did chlorpromazine appear to suppress the tendency of a septal animal to emerge from a home box. Even this effect i s a dubious one, however, since the number of h a l f - e x i t s involved was small. As w e l l , had f u l l rather than half e x i t s been designated as the scoring c r i t e r i o n no affect whatsoever would appear - 35 -since no animal actually accomplished a f u l l e x i t . Inadequate dosage immediately comes to mind by way of explanation. At 0.2 mg. per 100 gm. of body weight, however, the dose u t i l i z e d i n Experiment I I equals or exceeds the amounts administered by most behavioural and physio-l o g i c a l investigators (Cornetsky and Bain, 1965; Pirch and Norton; 1966; Archer, 1954; Boyd and M i l l e r , 1954). Watson and Steinberg (1967) report that .2 mg/ 100 gm usually produces a very s l i g h t muscular f l a c i d i t y i n rats. A larger dose then may involve r i s k i n g a degree of muscular impairment that would negate other findings. I t i s int e r e s t i n g to note that i n the same study Watson and Steinberg found that this dosage of chlorpromazine f a i l s to i n h i b i t the hyperglycaemic response to stress. I t has been reported that chlorpromazine depresses general a c t i v i t y as measured i n a c t i v i t y cages (Kinnard and Carr, 1957) or wheels (Routtenberg and Kuznesoff, 1967) and that i t affects selected components of a c t i v i t y (e.g. s n i f f i n g ) while not affecting others (e.g. grooming) (Bindra and Bacon, 1959). Apparently, however, i f a more stimulus oriented form of a c t i v i t y related to the degree of fearfulness or aggressiveness i s examined as was i n the present study, chlorpromazine has no effect on either normal or septal animals. Possibly any depressant or other effects of the drug are masked by the l e v e l of arousal i n the subjects due to the experimental s i t u a t i o n . The effects of the lesions proper were varied and not necessarily consistent with previously reported findings. As f i r s t observed by Brady and Nauta (1953) and often thereafter, the septalectomized rats displayed very high resistance to capture and handling i n a de f i n i t e demonstration of septal rage. The same animals c l e a r l y manifested less exploratory behaviour than controls i n an open f i e l d s i t u a t i o n . However, Nielson, Mclver and Boswell (1965), Clody and Carlton (1968) and Douglas and Raphelson (1966) have a l l reported increased exploratory behaviour i n septal rats u t i l i z i n g measures other than open f i e l d behaviour. Their studies involved movement within or between small enclosed spaces. Singh (1966), on the other hand, has found that i n a s i t u a t i o n where rats may leave an open f i e l d and return to a home - 36 -cage, septal animals tend to remain i n the open f i e l d although they do not explore as much as controls. The Nielson et a l . study also revealed that lesioned animals show very l i t t l e a c t i v i t y i n an open f i e l d apparatus. I f we consider a l l of the preceeding data i n the l i g h t of present findings, i . e . that septal rats .... a) are more resistant to handling and capture b) traverse fewer squares i n an open f i e l d c) demonstrate fewer rears i n an open f i e l d d) may have a greater tendency to leave a home cage .... the following picture emerges. Septalectomized r a t s , unlike normal animals, apparently tend to attempt to leave small enclosed spaces, however, when placed i n a bright open space they are less active than controls. How this s i t u a t i o n can be interpreted i n terms of emotionality i s another matter. Low levels of exploratory a c t i v i t y i n an open f i e l d apparatus may be taken as an i n d i c a t i o n of t i m i d i t y or fearfulness (Valle, 1970). Another approach, however, would view i t as in d i c a t i v e of a cautious, aggressive animal. The concept of reduced response i n h i b i t i o n due to septal damage would not seem applicable here since absence of response f a c i l i t a t i o n rather than i n h i b i t i o n seems to be the key factor. On the other hand, this concept would explain the tendency to be active i n or to leave small enclosed spaces. We have often observed septal rats to leap out of open colony cages, something rarely seen i n normal ra t s . This l a t t e r suggestion i s highly speculative of course, and serves mainly to i l l u s t r a t e the d i f f i c u l t y i n i n t e r -preting animal behaviour i n e s s e n t i a l l y subjective human terms such as f e a r f u l and fearless. Experiment I I , then, does not allow for s p e c i f i c conclusions. The fact that behavioural indices of emotionality do not corelate w e l l with each other i s borne out to a certain extent. In general i t would seem to lend support to a more physiological approach to the effects of neural damage on emotionality. - 37 -This approach as employed i n Experiment I seems to have produced data c l e a r l y contradicting the concept of septal hyperemotionality. Con-f l i c t i n g evidence has been noted as w e l l , however, and as mentioned pre-viously there ex i s t various untested measures which may be u t i l i z e d to resolve this c o n f l i c t . BIBLIOGRAPHY Anand, B.K. 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Journal of Comparative  and Physiological Psychology. 58, 1964, 217-224. / - 42 -Schwartzbaum, J.S. and Gay, P.E. Interacting behavioural effects of septal and amygdaloid lesions i n the r a t . Journal of  Comparative and Physiological Psychology. 61(1), 1966, 59-65 Selye, H. Stress. 1950 Acta, Montreal. Singh, D. Factors underlying emotionality produced by i n f a n t i l e stimulation and septal lesions. Psychological Reports. 19, 1966, 779-785. Thomas, G.J., Moore, R.Y., Harvey, J.A. and Hunt, F. Relations between the behavioural syndrome produced by lesions i n the septal region of the forebrain and maze learning of the r a t . Journal  of Comparative and Physiological Psychology. 52, 1959, 527-532. Va l l e , F.P. Effects of s t r a i n , sex and i l l u m i n a t i o n on open-field behaviour of rats. American Journal of Psychology. 83(1), 1970, 103-111. Vanderwolf, CH. Effect of combined medial thalamic and septal lesions on active-avoidance behaviour. Journal of Comparative and  Physiological Psychology. 58, 1964, 31-37 Watson, R.H.J, and Steinberg, H. Effects of drugs on hyperglycaemia induced by stress i n rats. Neuro-Psychopharmacology. 12, 1967, 427-430. Wood, CD. Behavioural changes following discrete lesions of temporal lobe structures. Neurology. 8, 1958", 215-220. -4 -3-A P P E N D I X A H i s t o l o g i c a l reconstructions of se p t a l area damage i n lesioned subjects i n experiments I.and I I . Four representative sections per brain are shown 6.2, 7 . 0 , 7.8, and 8.6 mm. a n t e r i o r to bregma r e s p e c t i v e l y . x J A 8 . 6 Septal 1 ( • ' i A 7.8 1 i . 4 I 1 1 1 1 1 I I _ ] I 0 1 2 3 4 5 6 7 8 f " • , ' • ' I • I + 7 r +G A 8 6 Expt. 1 Septal 5 < • A 8 . 6 Expt. 1 Septal 8 A 8 . 6 + 2 Expt. 1 Septal 9 A 6.2 >. H r Expt. 2 Septal 1 'I A 7.0 Expt. 2 Septal 2 A 8 6 Septal 2 +6 + 5 + 4 h A 6.2 Expt. 2 Septal 3 1 ( - -« • -1 I + 7 r A 7.6 Expt. 2 Septal 3 •K7 A 8 . 6 Expt. 2 Septal 3 + 7 A 8 . 6 Expt. 2 Septal 5 + 7 r A 7 . 8 Expt. 2 Septal 6 6 i - 5 A 7 . 8 8 

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