Xu X, Domino E F
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0626.
Pharmacol Biochem Behav. 1994 Mar;47(3):603-8. doi: 10.1016/0091-3057(94)90165-1.
Chronic administration of a psychomotor stimulant has been shown to produce progressively enhanced effects, a phenomenon called "reverse tolerance" or sensitization. The present study reexamined the effects of the daily injection of phencyclidine on locomotor activity and stereotypy in rats, and investigated whether drug-environment conditioning was necessary for the development of behavioral sensitization and whether (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]cyclohepten-5,1 0-imine hydrogen maleate (MK-801, dizocilpine) blocked behavioral sensitization to phencyclidine. Female Sprague-Dawley rats were used. Locomotor activity and stereotypy were measured automatically with the Digiscan system. The results confirmed an earlier finding that four daily injections of phencyclidine induced sensitization to both locomotor activity and stereotypy. The development of behavioral sensitization did not require drug-environment conditioning. Moreover, MK-801 did not block behavioral sensitization to phencyclidine. The results of the present study suggest that the neuronal mechanisms underlying sensitization to phencyclidine are different from those underlying sensitization to amphetamine and cocaine.
长期给予精神运动性兴奋剂已被证明会产生逐渐增强的效应,这一现象被称为“反向耐受”或敏感化。本研究重新审视了每日注射苯环利定对大鼠运动活动和刻板行为的影响,并调查了药物 - 环境条件作用对于行为敏感化的发展是否必要,以及(5R,10S)-(+)-5 - 甲基 - 10,11 - 二氢 - 5H - 二苯并[a,b]环庚烯 - 5,10 - 亚胺马来酸氢盐(MK - 801,地佐环平)是否能阻断对苯环利定的行为敏感化。使用雌性斯普拉格 - 道利大鼠。运动活动和刻板行为通过Digiscan系统自动测量。结果证实了早期的一项发现,即每日注射四次苯环利定可诱导对运动活动和刻板行为的敏感化。行为敏感化的发展不需要药物 - 环境条件作用。此外,MK - 801并未阻断对苯环利定的行为敏感化。本研究结果表明,对苯环利定敏感化的神经机制与对苯丙胺和可卡因敏感化的神经机制不同。