Involvement of dopamine in the nucleus accumbens and prefrontal cortex in cocaine-associative learning

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Ikegami, Aiko

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Stimuli formerly associated with cocaine-taking behavior are known to elicit physiological changes and craving in cocaine-dependent individuals. This is a result of learned associations between an environmental stimulus and the effects of cocaine, and is believed to be a major factor that leads to relapse in recovering cocaine addicts. A precise neural mechanism underlying how cocaine-paired stimuli produce craving and drug-taking behavior is currently unknown. Synaptic plasticity is known as a neural basis for associative learning. A modulatory role of a neurotransmitter, dopamine (DA), in synaptic plasticity has been implicated. Moreover, recent studies indicate that DA is particularly important during acquisition of associative learning, but less important as learning progresses. Yet, this notion has not been fully investigated using cocaine as a reinforcer. The nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC) brain regions, are both largely implicated in drug addiction. Using an animal model of drug- taking behavior in conjunction with an in vivo microdialysis technique, the dissertation experiments determined the involvement of DA in during distinctive stages of cocaine associative learning. Results from the experiments showed that NAcc DA was responsive to cocaine-paired stimuli during early, but not the late stages of cocaine associative learning while responsiveness of mPFC DA to cocaine-paired stimuli was enhanced with extended conditioning experience. The results indicate that brain areas responsive to conditioned stimuli transfers as associative learning progresses. These findings suggest that a dynamic role of DA in distinctive brain regions should be taken into account during treatment and relapse prevention of cocaine addiction.