Cocaine differentially affects benzodiazepine receptors in discrete regions of the rat brain: persistence and potential mechanisms mediating these effects.

The effects of cocaine on benzodiazepine (BZD) receptor binding in the rat brain were investigated using homogenate receptor binding and quantitative autoradiography. Although acute cocaine injections produced little or no effect on BZD binding sites, chronic administration resulted in differential effects in brain regions associated with the mesocorticolimbic and nigro-striatal dopaminergic neuronal system, respectively. BZD receptor binding was increased significantly in the caudate nucleus and decreased in the substantia nigra for up to 2 days after the final injection, whereas binding was decreased in the nucleus accumbens and medial prefrontal cortex and increased in the ventral tegmental area after daily injections of cocaine for 15 days. Binding was altered significantly only in the medial prefrontal cortex and ventral tegmental area 2 weeks after the final cocaine injection. Intraventricular injections of 6-hydroxydopamine attenuated or reversed the cocaine-induced changes in BZD receptor binding, suggesting that these effects were mediated, in part, through the effects of the drug on dopaminergic neuronal activity. Dopamine may be involved in the regulation of BZD receptors because 6-hydroxydopamine administration produced changes in BZD receptor binding in saline-treated rats that were generally in the opposite direction to those observed in cocaine-treated rats following sham treatment.