Clinical Neurobiology of Serotonin and Addiction

The purpose of this study is to examine the relationship between 5-HT2R function, impulsivity and cue reactivity in cocaine dependent subjects and healthy controls and examine specific effects of escitalopram and mirtazapine on impulsivity and cue reactivity in human cocaine users.

Specific Aim 1: We will test the hypothesis that cocaine-dependent subjects will exhibit greater impulsivity than controls as determined by a battery of impulsivity measures and that impulsivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce impulsivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression. Specific Aim 2: We will test the hypothesis that cocaine-dependent subjects will exhibit greater cue reactivity than controls as determined by a modified Stroop task, and that cue reactivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce cue reactivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression. Specific Aim 3: We will test the hypothesis that specific polymorphisms in the 5-HT2AR and/or 5-HT2CR will predict baseline impulsivity and/or cue reactivity as well as treatment response to serotonergic medications in cocaine-dependent subjects.