Ujike H, Kuroda S, Otsuki S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Eur J Pharmacol. 1996 Jan 25;296(2):123-8. doi: 10.1016/0014-2999(95)00693-1.
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.
研究了假定的σ受体拮抗剂BMY-14802（α-（4-氟苯基）-4-（5-氟-2-嘧啶基）-1-哌嗪）、利咪唑和SR-31742A（顺式-3-（六氢氮杂环庚烷-1-基）-1-（3-氯-4-环己基苯基）丙烯-1）对反复给予可卡因诱导的行为敏化发展的影响。大鼠腹腔注射15mg/kg可卡因可引起中度多动，主要表现为嗅探和竖毛。可卡因的这些急性作用几乎不受σ受体拮抗剂共同给药的影响，只是BMY-14802增强了可卡因诱导的运动，但不显著。虽然反复给予可卡因会导致刻板行为逐渐增加并产生敏化，但所测试的每种σ受体拮抗剂均减弱了对可卡因敏化的发展。在戒断后单独用可卡因进行激发试验证实了σ受体拮抗剂对可卡因诱导的敏化的这些预防作用。这些结果与我们先前的研究结果一致，该研究表明BMY-14802可阻断对另一种精神兴奋剂甲基苯丙胺的敏化。因此，σ受体在精神兴奋剂诱导的敏化现象的发展中起关键作用，而精神兴奋剂诱导的敏化现象是精神分裂症的药理学模型。
