ALTERATIONS IN THE DOPAMINERGIC RECEPTOR SYSTEM AFTER CHRONIC ADMINISTRATION OF COCAINE

Several studies suggest that one of the most important factors contrib uting to cocaine dependence is an alteration in the actions of the neu rotransmitter dopamine in the central nervous system. In order to unde rstand some of the neuroreceptor consequences of cocaine administratio n, groups of rats were injected with cocaine (2 daily doses of 15 mg/k g) for 1 to 21 days. Binding of H-3!cocaine, H-3!SCH23390, H-3!racl opride, and H-3!BTCP in striatal and cortical tissue from the treated animals was compared to controls. H-3!Cocaine binding was increased by the drug in the striatum and cortex at days 14 and 21, respectively . The binding of H-3!SCH23390 to D1 dopamine receptors was significan tly increased at day 3 of cocaine exposure. In striatal membranes, H- 3!BTCP binding to dopamine uptake sites was significantly increased af ter day 7, whereas binding in cortical membranes was increased from da y 1. H-3!Raclopride binding to D2 dopamine receptors remained unchang ed throughout the study in both cortical and striatal tissues. These r esults indicate that repeated exposure to cocaine produces an upregula tion (possible supersensitivity) in cortical D1, cocaine, and DA-uptak e sites which occurs in a time-dependent manner. These increases are c oupled with an upregulation in striatal D1, cocaine, and DA-uptake sit es, without simultaneous changes in D2 receptors. Thus, cocaine's effe cts are not uniformly distributed across all brain regions, but rather are focused within areas of the dopamine system. (C) 1993 Wiley-Liss, Inc.