Pascucci T, Cioli I, Pisetzky F, Duprè S, Spirito A, Nencini P
Institute of Medical Pharmacology, University of Rome 'La Sapienza', P.le A. Moro 5, Rome, 00185, Italy.
Pharmacol Res. 1999 Oct;40(4):333-8. doi: 10.1006/phrs.1999.0524.
Acamprosate (calcium acetylhomotaurinate) is a GABA derivative that prevents drinking relapses in a significant number of alcoholics. Since little is known about the interaction of acamprosate with other addictive drugs, we studied the effects of this agent (as sodium salt) in two groups of rats trained to discriminate, respectively, morphine (1.7 mg kg(-1)i.p.) or amphetamine (0.5 mg kg(-1)i.p.) from solvent in a two-lever fixed ratio 30 operant behaviour reinforced by water access. Accordingly to the finding that acamprosate inhibits the action of excitatory aminoacids, its effects were compared with those of dizocilpine (MK-801), an NMDA antagonist. Results show that acamprosate (170 and 320 mg kg(-1)i.p. ) produced a slight, and not significant, shift to the left of generalization curves of both morphine and amphetamine without affecting response rates. In contrast, MK-801 potentiated response rate effects of both morphine and amphetamine without affecting their generalization curves. As far as discriminative stimuli participate in the relapsing process of addiction, our results do not predict a role of acamprosate in the prevention of amphetamine or morphine abuse relapsing.
阿坎酸(钙乙酰高牛磺酸)是一种γ-氨基丁酸衍生物,可使大量酗酒者防止复饮。由于对阿坎酸与其他成瘾性药物的相互作用了解甚少,我们在两组经训练能在以获得水强化的双杠杆固定比率30操作性行为中分别区分吗啡(1.7毫克/千克腹腔注射)或苯丙胺(0.5毫克/千克腹腔注射)与溶剂的大鼠中研究了该药物(钠盐形式)的作用。鉴于阿坎酸抑制兴奋性氨基酸作用的这一发现,将其作用与NMDA拮抗剂地佐环平(MK-801)的作用进行了比较。结果显示,阿坎酸(170和320毫克/千克腹腔注射)使吗啡和苯丙胺的泛化曲线均轻微左移,但不显著,且不影响反应率。相反,MK-801增强了吗啡和苯丙胺的反应率效应,但不影响它们的泛化曲线。就辨别性刺激参与成瘾复发过程而言,我们的结果并未预测阿坎酸在预防苯丙胺或吗啡滥用复发方面的作用。