Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats
Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats
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DOI：
10.1038/sj.bjp.0706228
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发表时间：
2005-07-01
影响因子：
7.3
通讯作者：
Araki, H
中科院分区：
文献类型：
--
作者：
Kawasaki, Y;Jin, CY;Araki, H
1 急性阿片依赖戒断的负面动机成分背后的神经生物学机制尚不清楚。2 我们的目标是确定谷氨酸能系统是否参与急性依赖性大鼠吗啡戒断的动机成分，并且这种参与与多巴胺能神经传递相关。3 我们检查了各种谷氨酸受体拮抗剂对纳洛酮诱发的条件性位置厌恶 (CPA) 的影响。 24 小时前接触吗啡。此外，还研究了多巴胺受体拮抗剂氟哌啶醇预处理对谷氨酸受体拮抗剂作用的影响。 4 CPA 被所有检查的谷氨酸受体拮抗剂以剂量依赖性方式减弱，包括 NMDA 受体拮抗剂 (+)-5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺马来酸盐 (MK-801) 和盐酸苯环己哌啶 (PCP)、AMPA 受体拮抗剂 1-(4-氨基苯基)4-甲基-7,8-亚甲二氧基-5H-2,3-苯二氮卓盐酸盐 (GYKI 52466) 和代谢型受体拮抗剂 (+/-)-2-氨基-3-膦酰基丙酸 (AP-3) 和 (+/-)-α-甲基-4-羧基苯基甘氨酸 (MCPG)。 MK-801、GYKI 52466 和 MCPG 的作用被氟哌啶醇阻断。 5 这些结果表明，涉及多类受体的谷氨酸能系统在急性吗啡依赖戒断的动机成分中发挥作用，并且谷氨酸能系统的功能与多巴胺能神经传递密切相关。
1 The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood.2 Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission.3 We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated.4 CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10- imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride ( GYKI 52466), and metabotropic receptor antagonists (+/-)-2-amino-3-phosphonopropionic acid (AP-3) and (+/-)-alpha-methyl-4-carboxyphenylglycine ( MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol.5 These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.