sigma Receptor antagonists block the development of sensitization to cocaine.
The effects of putative sigma receptor antagonists, BMY-14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine), 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 sigma 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 sigma receptor antagonists tested attenuated the development of sensitization to cocaine. These prophylactic effects of sigma 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, sigma receptors play a crucial role in the development of the psychostimulant-induced sensitization phenomenon, which is a pharmacological model of schizophrenia.
Ujike
H
H
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Kuroda
S
S
Otsuki
S
S
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*
D014150:Antipsychotic Agents; D001381:Azepines; D017480:Receptors, sigma; C080238:3-(hexahydroazepin-1-yl)-1-(3-chloro-4-cyclohexylphenyl)-1-propene hydrochloride; D003042:Cocaine