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Investigations of the neurobiological and behavioural actions of cocaine

University of British Columbia

Although once considered a benign recreational stimulant, cocaine is now recognized to possess substantial abuse potential with considerable medical and social consequences. Accordingly, these experiments examined the behavioural and neurobiological effects of cocaine in the rat. The behavioural and neurochemical interactions between cocaine and buprenorphine were examined using a conditioned place preference (CPP) procedure and in vivo microdialysis. Cocaine and buprenorphine both elicited CPP; moreover, these drugs interacted to produce significantly larger CPPs when given in combination. Both cocaine and buprenorphine increased interstitial concentrations of dopamine in the nucleus accumbens; the effect of cocaine was potentiated by the coadministration of buprenorphine. Taken as a whole, these results indicate that buprenorphine can interact with cocaine in as ynergistic manner. The ability of stimuli previously paired with cocaine to elicit similar neurochemical changes as cocaine was assessed by in vivo microdialysis. Although acutely administered cocaine produced a significant increase in interstitial dopamine concentrations in the nucleus accumbens, the presentation of a cocaine-paired environment did not. Despite the absence of a conditional neurochemical effect, significant conditioned locomotion was observed. These data do not support the hypothesis that stimuli paired with cocaine produce their behavioural effects by eliciting similar neurochemical effects as cocaine. To understand better the neurobiology of cocaine-induced environment-specific conditioning, expression of c-Fos, a putative marker of neuronal activity, was examined in the forebrain of rats exposed to an environment in which they had previously received cocaine. Compared to saline-treated controls, cocaine produced an increase in locomotor behaviour that was accompanied by an increase in c-Fos expression within specific limbic regions, as well as the basal ganglia. Exposure of rats to the cocaine-paired environment also produced an increase in locomotion that was associated with an increase in c-Fos expression within specific limbic regions, but not within the basal ganglia. These findings suggest that specific limbic regions exhibit increased neuronal activation during the presentation of cocaine-paired cues and may be involved in the formation of associations between cocaine's stimulant actions and the environment in which the drug administration occurred. Given the large body of evidence implicating the amygdaloid complex in the learning of stimulus-reward associations, the effects of quinolinic acid lesions of the amygdala on cocaine-induced conditional locomotion and CPP were examined. Although destruction ofthe amygdala did not affect basal locomotion, cocaine-induced locomotion or cocaine-induced conditional locomotion, cocaine-induced CPP was completely blocked by the amygdaloid lesions. These data demonstrate that cocaine-induced stimulus-reward conditioning can be differentially affected by lesions of the amygdala. These studies provide a further understanding of the neurobiology of cocaine's behavioural actions. The implications for the treatment of cocaine abuse are discussed.

Thesis/Dissertation

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2008-09-11

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http://hdl.handle.net/2429/1873

Neuroscience

University of British Columbia

UBCV

DSpace