Bedingfield J B, Calder L D, Thai D K, Karler R
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Pharmacol Biochem Behav. 1997 Feb;56(2):305-10. doi: 10.1016/s0091-3057(96)00331-0.
Previous results of pharmacological studies of the mechanisms of amphetamine- and cocaine-induced stereotypy in the mouse suggest the involvement of dopaminergic, glutamatergic and GABAergic systems in the striatum. The present experiments were designed to evaluate pharmacologically the role of these neuroeffector systems in behavioral sensitization. Whether administered systemically or in the striatum, pretreatment with the neurotransmitter antagonists, sulpiride, bicuculline and CPP, blocked both the induction and the expression of behavioral sensitization. Efforts to induce sensitization or evoke expression with intrastriatal microinjections of amphetamine, NMDLA or THIP were not successful. The data indicate that these three neuroeffector systems interact at the level of the striatum to mediate the induction and expression of behavioral sensitization to amphetamine. The results are discussed in light of our previous reports and lead to the conclusion that two groups of drugs that affect sensitization can be defined: (1) antagonists of the dopaminergic, GABAergic and glutamatergic systems which block the acute effects of amphetamine as well as the induction and expression of sensitization and (2) another group of drugs which antagonize only sensitization-associated phenomena. The mouse data suggest that both the induction and the expression of sensitization involve not only multiple loci but also novel neuroeffector systems.
以往对苯丙胺和可卡因诱导小鼠刻板行为机制的药理学研究结果表明，纹状体中的多巴胺能、谷氨酸能和γ-氨基丁酸能系统参与其中。本实验旨在从药理学角度评估这些神经效应系统在行为敏化中的作用。无论是全身给药还是纹状体内给药，用神经递质拮抗剂舒必利、荷包牡丹碱和CPP进行预处理，均能阻断行为敏化的诱导和表达。通过纹状体内微量注射苯丙胺、N-甲基-D-天冬氨酸（NMDLA）或4,5,6,7-四氢异喹啉-3-醇（THIP）来诱导敏化或激发其表达的尝试均未成功。数据表明，这三种神经效应系统在纹状体水平相互作用，以介导对苯丙胺行为敏化的诱导和表达。根据我们之前的报告对结果进行了讨论，得出的结论是，可以定义两类影响敏化的药物：（1）多巴胺能、γ-氨基丁酸能和谷氨酸能系统的拮抗剂，它们既能阻断苯丙胺的急性效应，也能阻断敏化的诱导和表达；（2）另一类仅拮抗与敏化相关现象的药物。小鼠实验数据表明，敏化的诱导和表达不仅涉及多个位点，还涉及新的神经效应系统。
