Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5814010 | Neuropharmacology | 2015 | 11 Pages |
Abstract
The serotonin system is intimately linked to both the mediation of anxiety and long-term effects of cocaine, potentially through interaction of inhibitory 5-HT2C receptor and gamma-aminobutyric acid (GABA) networks. This study characterized the function of the dorsal raphe (DR) 5-HT2C receptor and GABA network in anxiety produced by chronic cocaine withdrawal. C57BL/6 mice were injected with saline or cocaine (15Â mg/kg) 3 times daily for 10 days, and tested on the elevated plus maze 30Â min, 25Â h, or 7 days after the last injection. Cocaine-withdrawn mice showed heightened anxiety-like behavior at 25Â h of withdrawal, as compared to saline controls. Anxiety-like behavior was not different when mice were tested 30Â min or 7 days after the last cocaine injection. Electrophysiology data revealed that serotonin cells from cocaine-withdrawn mice exhibited increased GABA inhibitory postsynaptic currents (IPSCs) in specific DR subregions dependent on withdrawal time (25Â h or 7Â d), an effect that was absent in cells from non-withdrawn mice (30Â min after the last cocaine injection). Increased IPSC activity was restored to baseline levels following bath application of the 5-HT2C receptor antagonist, SB 242084. In a separate cohort of cocaine-injected mice at 25Â h of withdrawal, both global and intra-DR blockade of 5-HT2C receptors prior to elevated plus maze testing attenuated anxiety-like behavior. This study demonstrates that DR 5-HT2C receptor blockade prevents anxiety-like behavior produced by cocaine withdrawal, potentially through attenuation of heightened GABA activity, supporting a role for the 5-HT2C receptor in mediating anxiety produced by cocaine withdrawal.
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Authors
Caryne P. Craige, Stacia Lewandowski, Lynn G. Kirby, Ellen M. Unterwald,