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Title: Neural and neurochemical mechanisms of cocaine-seeking behaviour
Author: Ito, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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The research in this thesis investigated the role of different dorsal and ventral striatal regions and their dopaminergic innervations in cocaine-seeking and -taking behaviour under the control of a drug-associated conditioned stimulus (CS). Neurochemical correlates of cocaine-seeking behaviour in rats were first determined by conducting in vivo microdialysis within the nucleus accumbens (NAcc) core and shell subregions during; (1) cocaine self-administration under a second-order schedule of reinforcement whereby cocaine-seeking behaviour was maintained by response-contingent presentations of a drug associated cue and (2) non-contingent presentations of the drug cue. While the results confirmed the involvement of NAcc dopamine (DA) in the pharmacological effects of cocaine, they also revealed a selective DA response in the core, as opposed to the shell, region of the NAcc during non-contingent CS exposure. The same DA system however, did not appear to mediate the ability of the CS to maintain cocaine-seeking behaviour since there was no DA response in either of the NAcc regions to response-contingent CS presentations. The dynamics of DA changes in response to non-contingent CS presentations and cocaine-seeking behaviour in the presence of response-contingent CS presentations were also studied using identical procedures in the dorsolateral striatum, a region implicated in stimulus-response (habit) learning. A robust DA response was observed during the period of cocaine-seeking behaviour under the guidance of the CS, but not during non-contingent presentations of the CS; results that are doubly dissociable from those of the NAcc core region. In the last phase of the studies reported in this thesis, the basis of the differential DA response to non-contingent presentations of the CS in the NAcc core was further investigated by assessing the impact of selectively lesioning the NAcc core and shell subregions on the acquisition of cocaine self-administration, both under a continuous reinforcement schedule (CRf) and a second order schedule of reinforcement.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available