UBC Theses and Dissertations
The role of dopamine in preparatory and consummatory defensive behaviours Blackburn, James Robert
The effects of neuroleptic drugs on avoidance and freezing behaviours of rats were examined in a series of experiments. In Chapter I it was found that the acquisition of a one-way avoidance response was precluded by a dose of haloperidol (0.15 mg/kg) that did not prevent escape responses and that did not initially disrupt performance of a previously acquired response. The atypical neuroleptics thioridazine (10-50 mg/kg) and clozapine (1.25-10.0 mg/kg) did not preclude acquisition of the response and had nonspecific effects on performance of an acquired response. In contrast, metoclopramide (5.0 mg/kg), like haloperidol, precluded acquisition of avoidance responding without initially disrupting performance. Given the clinical profiles of these drugs, these results suggest that disruption of avoidance responding by neuroleptic drugs may be more closely related to their capacity to produce extrapyramidal side effects than to their ability to relieve psychotic symptoms. Chapter II examined the effect of metoclopramide on performance of avoidance responses after various training regimes. Metoclopramide effects were attenuated by a single training session of 10 trials, or, if the tone warning signal had previously been paired with shock, as few as 5 trials. No prophylactic effect of pretraining was observed if the rats were given noncontingent safety conditioning consisting of pairings of shock termination with the safe side of the apparatus plus a light cue. However, metoclopramide had little impact if pretraining consisted of prior tone-shock pairings plus the opportunity to escape from unsignalled shock in the avoidance apparatus. These results exclude the possibility that attenuation of metoclopramide effects is due to overtraining of the avoidance response. Chapter III established that freezing responses to shock are potentiated by metoclopramide, although the magnitude of freezing responses to a conditional stimulus signalling shock was not enhanced significantly. Following up on this discovery, Chapter IV determined that the disruptive effect of metoclopramide on avoidance responding was enhanced by the presence of additional shock or shock cues. It was concluded that the enhancement of freezing by metoclopramide contributes to the deficit in avoidance responding observed following metoclopramide treatment. These results were interpreted as supporting a hypothesis that central dopamine systems are involved in the execution of preparatory responses directed towards distal stimuli, but not in consummatory responses directed towards diffuse local or internal cues.
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