Cocaine Addiction and the Role of Serotonin in Orbitofrontal Cortex Function

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During the past fiscal year we have successfully recorded from OFC neurons in brain slices obtained from rats, and have examined the effects of serotonin (5-HT) on these neurons. In addition, we have established that there is a deficit in baseline glutamate-mediated synaptic transmission in rats trained to self-administer cocaine that lasts for many moths after this training is finished. This deficit in OFC synaptic transmission was associated with decreased performance in a Pavlovian overexpectation behavioral task that is known to be reliant upon intact OFC function. We also found that reversing this deficit could restore the overexpectatio behavior, supporting the hypothesis that altered synaptic function in the OFC is a primary outcome of cocaine addiction, that may lead to impaired decision making, and more generally cognition. Current studies are now focused upon the potential role that 5-HT plays in regulating OFC neuron activity, and whther cocaine experience alters this activity. These 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.