Differential Blockade of Chronic Versus Acute Effects of Intravenous Cocaine by Dopamine Receptor Antagonists

The objectives of this study were to investigate behavioral sensitization to repeated once daily IV injections of cocaine, and to determine whether dopamine receptor antagonists differentially block chronic versus acute cocaine effects. Acute cocaine (0.3-3.0 mg/kg) produced a dose-dependent increase in both horizontal and stereotypic movements in male Sprague-Dawley rats. Repeated once daily injections of 1 or 3 mg/kg of cocaine augmented these effects. Pretreatment with either the D2 dopamine receptor antagonist haloperidol (0.03-0.3 mg/kg) or the D1 dopamine receptor antagonist R(+)-SCH-23390 (0.003-0.1 mg/kg) dose dependently attenuated cocaine's behavioral effects in both sensitized and cocaine-naive animals. There was a rightward shift in the dose-effect relationship of these antagonists in blocking the expression of behavioral sensitization as compared to their ability to block the acute behavioral effects of cocaine. These results indicate that repeated once daily IV injections of cocaine produced behavioral sensitization and both D1 and D2 dopamine receptor antagonists attenuated the expression of this sensitization. The data also suggest that dopamine receptor antagonists were more potent in blocking cocaine's effects in cocaine-naive animals than in cocaine-sensitized animals.