sigma receptor antagonists block the development of sensitization to cocaine

The effects of putative a receptor antagonists, BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazime), rimcazole and SR-31742A (cis-3-(hexahydroazepin-1-yl)1-(3-chloro-4-cyclohexylphenyl)propene-1) on the development of behavioral sensitization induced by repeated administration of cocaine were investigated. Acute intraperitoneal injection of 15 mg/kg cocaine in rats induced moderate hyperactivity which mainly consisted of sniffing and rearing. These acute effects of cocaine were hardly affected by co-administration of the a receptor antagonists, except that BMY-14802 enhanced, but not significantly, cocaine-induced locomotion. While repeated cocaine administration induced a progressive increase in stereotyped behaviors and resulted in sensitization, every a receptor antagonists tested attenuated the development of sensitization to cocaine. These prophylactic effects of a receptor antagonists against cocaine-induced sensitization were confirmed by the challenge test with cocaine alone after an abstinence. These results were consistent with results of our previous study which revealed that BMY-14802 blocked the sensitization to methamphetamine, another psychostimulant. Therefore, a receptors play a crucial role in the development of the psychostimulant-induced sensitization phenomenon, which is a pharmacological model of schizophrenia.