Alterations in the dopaminergic receptor system after chronic administration of cocaine.
Several studies suggest that one of the most important factors contributing to cocaine dependence is an alteration in the actions of the neurotransmitter dopamine in the central nervous system. In order to understand some of the neuroreceptor consequences of cocaine administration, groups of rats were injected with cocaine (2 daily doses of 15 mg/kg) for 1 to 21 days. Binding of [3H]cocaine, [3H]SCH23390, [3H]raclopride, and [3H]BTCP in striatal and cortical tissue from the treated animals was compared to controls. [3H]Cocaine binding was increased by the drug in the striatum and cortex at days 14 and 21, respectively. The binding of [3H]SCH23390 to D1 dopamine receptors was significantly increased at day 3 of cocaine exposure. In striatal membranes, [3H]BTCP binding to dopamine uptake sites was significantly increased after day 7, whereas binding in cortical membranes was increased from day 1. [3H]Raclopride binding to D2 dopamine receptors remained unchanged throughout the study in both cortical and striatal tissues. These results indicate that repeated exposure to cocaine produces an upregulation (possible supersensitivity) in cortical D1, cocaine, and DA-uptake sites which occurs in a time-dependent manner. These increases are coupled with an upregulation in striatal D1, cocaine, and DA-uptake sites, without simultaneous changes in D2 receptors. Thus, cocaine's effects are not uniformly distributed across all brain regions, but rather are focused within areas of the dopamine system.
Alburges
M E
ME
Department of Pharmaceutical Sciences, North Dakota State University, Fargo 58105.
Narang
N
N
Wamsley
J K
JK
D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000493:pharmacokinetics / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D020891:Raclopride; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012457:Salicylamides / Q000493:pharmacokinetics / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D020891:Raclopride; D003042:Cocaine; D010622:Phencyclidine; D004298:Dopamine