zes 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.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
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Wright, Andrew M; Zapata, Agustin; Baumann, Michael H et al. (2016) Enduring Loss of Serotonergic Control of Orbitofrontal Cortex Function Following Contingent and Noncontingent Cocaine Exposure. Cereb Cortex :
Lucantonio, Federica; Takahashi, Yuji K; Hoffman, Alexander F et al. (2014) Erratum: Orbitofrontal activation restores insight lost after cocaine use. Nat Neurosci 17:1287
Lucantonio, Federica; Takahashi, Yuji K; Hoffman, Alexander F et al. (2014) Orbitofrontal activation restores insight lost after cocaine use. Nat Neurosci 17:1092-9