Dopamine Effects in Prefrontal Cortex in Models of Drug Abuse and Schizophrenia

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DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) contains a rich dopamine (DA) innervation. The majority of electrophysiological studies examining DA effects on the medial PFC (mPFC) in vitro have been performed in pre-adolescent rats. Given that it has recently been shown that dopaminergic regulation of mPFC function changes postpubertally, there is a present need to examine DA function in the PFC in adult animals. The mesocortical DA system is implicated in drug abuse and schizophrenia. Typically, increased excitability of mPFC pyramidal neurons has been documented after repeated cocaine administration. However, these studies used non-contingent administration in behavioral sensitization paradigms. Therefore, changes in PFC excitability after cocaine self-administration, a model of drug abuse behavior that better resembles human use, will be examined. Schizophrenia patients have been shown to have higher rates of substance abuse than the average population. Similarly, enhanced stimulant self-administration has been observed in animals with a neonatal ventral hippocampal lesion, a developmental animal model of schizophrenia. It remains to be determined what changes occur in cortical DA function in this rat model of schizophrenia after cocaine self-administration. The goal of these studies is to provide a foundation of work examining alterations in dopaminergic regulation of mPFC function in adult animals as related to schizophrenia-drug abuse comorbidity.