Calcagnetti D J, Keck B J, Quatrella L A, Schechter M D
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095.
Life Sci. 1995;56(7):475-83. doi: 10.1016/0024-3205(94)00414-n.
Conditioned place preference/aversion testing is a behavioral method believed capable of measuring the affective (positive, neutral or negative) properties of psychoactive drugs. Cocaine injections in rats reliably produces a positive place preference. Drugs that attenuate or block this effect of cocaine have obvious potential for developing treatments to address cocaine addiction as well as to add to the scientific understanding of the mechanism of cocaine's action at the cellular level. To date, six drugs have been reported to block the expression of a cocaine-induced conditioned place preference (CPP) and this review evidences the cocaine-induced CPP blockage by the two potent L-type calcium channel blockers, isradipine and nifedipine, the two serotonin-3 receptor antagonists, MDL72222 and ICS205-930, the delta opioid receptor selective antagonist naltrindole, and lastly, a mixed opioid agonist-antagonist buprenorphine. Additional evidence relating to the blockade of other cocaine behavioral effects by these putative blockers is addressed, where appropriate, from studies employing other procedures such as drug stimulus discrimination, self-administration, electrical brain stimulation and increases in locomotor activity. The significance of these findings is discussed in the context of their relevance to the development of treatment regimens to allow for cessation of cocaine abuse.
条件性位置偏爱/厌恶测试是一种行为学方法,被认为能够测量精神活性药物的情感(积极、中性或消极)特性。给大鼠注射可卡因可可靠地产生阳性位置偏爱。能够减弱或阻断可卡因这种作用的药物对于开发治疗可卡因成瘾的方法以及增进对可卡因在细胞水平作用机制的科学理解具有明显的潜力。迄今为止,已有六种药物被报道可阻断可卡因诱导的条件性位置偏爱(CPP)的表达,本综述证明了两种强效L型钙通道阻滞剂(伊拉地平与硝苯地平)、两种5-羟色胺-3受体拮抗剂(MDL72222与ICS205-930)、δ阿片受体选择性拮抗剂纳曲吲哚以及最后一种混合阿片激动剂-拮抗剂丁丙诺啡可阻断可卡因诱导的CPP。在适当情况下,从采用其他程序(如药物刺激辨别、自我给药、脑电刺激和运动活动增加)的研究中获取了与这些假定阻滞剂阻断其他可卡因行为效应相关的更多证据。在这些发现与开发允许停止可卡因滥用的治疗方案的相关性背景下,讨论了这些发现的意义。