Karler R, Calder L D, Thai L H, Bedingfield J B
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
Brain Res. 1994 Sep 26;658(1-2):8-14. doi: 10.1016/s0006-8993(09)90003-8.
The behavioral effects of amphetamine and cocaine are generally considered to be the result of their indirect dopaminergic activity. Recent reports, however, suggest that the activity of the psychomotor stimulants involves not only the dopaminergic but also the glutamatergic system. In the present study the role of the glutamate system in the action of the stimulants was investigated in mice with the use of glutamatergic agonists and antagonists administered either intraperitoneally or intracranially into the striatum. CPP, an NMDA-type glutamate antagonist, given systemically or intrastriatally, blocked stereotypy induced by either amphetamine or cocaine. These results represent pharmacological evidence that the glutamate system is an essential component in the expression of the stereotypic effect of the psychomotor stimulants, and that a locus of this action of glutamate is in the striatum. These conclusions were supported further by the observation that NMDLA administered focally into the striatum caused stereotypy which was indistinguishable from that produced by either amphetamine or dopamine. Stereotypy induced by amphetamine injected into the striatum was blocked by CPP or sulpiride administered either systemically or directly into the striatum; in contrast, stereotypy induced by NMDLA given into the striatum was blocked by CPP but not by sulpiride, regardless of whether the antagonists were presented systemically or into the striatum. The data suggest that stereotypy induced by amphetamine or cocaine is mediated by a dopaminergic activation of a glutamatergic system within the striatum.
苯丙胺和可卡因的行为效应通常被认为是其间接多巴胺能活性的结果。然而，最近的报告表明，精神运动性兴奋剂的活性不仅涉及多巴胺能系统，还涉及谷氨酸能系统。在本研究中，利用腹腔内或颅内注射到纹状体中的谷氨酸能激动剂和拮抗剂，在小鼠中研究了谷氨酸能系统在兴奋剂作用中的作用。全身性或纹状体内给予NMDA型谷氨酸拮抗剂CPP，可阻断苯丙胺或可卡因诱导的刻板行为。这些结果代表了药理学证据，即谷氨酸能系统是精神运动性兴奋剂刻板效应表达的重要组成部分，且谷氨酸这种作用的位点在纹状体。将NMDLA局部注射到纹状体中会引起刻板行为，这与苯丙胺或多巴胺产生的刻板行为无法区分，这一观察结果进一步支持了这些结论。全身性或直接注射到纹状体中的CPP或舒必利可阻断注射到纹状体中的苯丙胺诱导的刻板行为；相比之下，无论拮抗剂是全身性给予还是注射到纹状体中，注射到纹状体中的NMDLA诱导的刻板行为可被CPP阻断，但不能被舒必利阻断。数据表明，苯丙胺或可卡因诱导的刻板行为是由纹状体内谷氨酸能系统的多巴胺能激活介导的。
