Cocaine Addiction and the Role of Serotonin in Orbitofrontal Cortex Function

National Institute On Drug Abuse

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Abstract

A manuscript is currently in review that summarizes the observations we have made in these studies in which we compared 5-HT receptor function in the orbitofrontal cortex (OFC) of rats receiving cocaine through self-administration (CSA) or, passively, through yoked administration (CYA). In summary, using whole-cell electrophysiology in brain slices, we found that physiological effects of 5-HT1A and 5-HT2A receptor activation were severely reduced following withdrawal of either CSA or CYA. Moreover, these reduced effects of 5-HT at these receptors persisted for many weeks after cocaine withdrawal, suggesting they may be involved in long-term aspects of cocaine addiction, such as craving. As 5-HT in the OFC is implicated in behavioral flexibility, learning and other cognitive abilities, our experiments will provide novel information as to the role that 5-HT plays in cocaine addiction, and in the impaired decision-making exhibited during cocaine addiction and withdrawal. In addition, since 5-HT is linked to several neuropsychiatric disorders, such as depression, anxiety, dementia, impulsive-aggression disorder (IAD), obsessive-compulsive disorder (OCD), and post-traumatic stres disorder (PTSD), these experiments should provide valuable information as to the clinical utility of targeting the 5-HT system in the OFC as potential therapies.