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The role of inhibitory mechanisms in habituation and sensitization of the flexor reflex MacDonald, John Ferguson

Abstract

Several authors have suggested that the reticular formation may act as a generator of behavioural inhibition. Furthermore, they have implied that this inhibition may progressively reduce evoked behaviour leading to behavioural habituation,(Hernandez-Peon, 1960; Sokolov, 1963; Stein, 1966). Stein (1966) proposed that recurrent inhibition of the reticular formation might be responsible for habituation of behavioural arousal. Wall (1970) presented the hypothesis that PTP of inhibitory synapses within the flexor reflex pathway might cause habituation of this reflex. However, experiments performed upon the spinal cat have not indicated a role for inhibition in habituation of the flexor reflex (Spencer, et al., 1966c; Groves and Thompson, 1973). A more reasonable explanation for habituation of this reflex in the spinal animal is a reduction in the efficacy of excitatory synapses within the direct reflex pathways (Farel, et al., 1973). Habituation of the flexor reflex is not identical in the spinal and intact rat (Pearson and Wenkstern, 1972). Habituation is more readily observed in the intact rat. This thesis has demonstrated that habituation of the flexor reflex is retarded but not prevented by the infusion of drugs which are known to antagonize inhibition (strychnine and bicuculline) provided the spinal cord is not transected. This was not the case for habituation of this reflex in the spinal rat. Indeed, the infusion of strychnine actually facilitated habituation in the spinal rat. Spontaneously active spinal interneurones were progressively inhibited (inhibitory build-up) by repeated cutaneous stimulation. This build-up of inhibition was greater with intense stimuli than with weak stimuli. However, a similar build-up of inhibition was not found after transection of the spinal cord. Inhibition itself tended to habituate in the spinal rat regardless of the intensity of the stimuli. The injection of strychnine eliminated inhibitory buildup in the intact rat in half of the interneurones tested but was ineffective in the remaining interneurones. Decerebration releases a tonic inhibition of the flexor reflex mediated by the reticular formation (Holmqvist and Lundberg, 1961). This thesis has demonstrated that habituation of the flexor reflex is much more pronounced in the decerebrate than in the spinal rat provided intense stimuli are employed. This evidence suggests that the reticular formation may be responsible for the genesis of inhibitory build-up. A similar build-up of inhibition of spinal activity has been shown following repetitive stimulation of the reticular formation (Abrahams, 1974; Haber and Wagman, 1974). The decrement of the flexor reflex related to a build-up of inhibition was only apparent when the intensity of the stimuli was noxious (possibly painful) and it may represent a mechanism for adaptation to pain. Serotonergic systems and the raphe nuclei are associated with an inhibition of behavioural arousal and the inhibition of pain. This thesis has shown that lesions of the nucleus raphe dorsalis and pre-treatment with p-CPA facilitate habituation of the flexor reflex relative to the intact animal (not treated with p-CPA). It is suggested that the raphe nuclei inhibit the reticular neurones responsible for the genesis of inhibitory build-up. Habituation of the flexor reflex in the spinal rat is best explained by a mechanism of reducing synaptic efficacy. However, intersegmental inhibitory mechanisms may be capable of modulating the amplitude of the reflex which in turn may alter the degree of habituation. Furthermore, the decrement of inhibition observed in the spinal rat may be responsible for long term sensitization of the flexor reflex.

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