Boegman R J, Vincent S R
Department of Pharmacology-Toxicology, Queen's University, Kingston, Ontario, Canada.
Synapse. 1996 Jan;22(1):70-7. doi: 10.1002/(SICI)1098-2396(199601)22:1<70::AID-SYN8>3.0.CO;2-F.
The psychostimulant drugs amphetamine and cocaine induce the expression of immediate early genes, such as c-fos, in the striatum via D1 dopamine receptor activation. This occurs primarily in the striato-nigral neurons. Conversely, neuroleptic drugs, such as haloperidol, which block D2-type dopamine receptors, induce c-fos expression in striatal neurons projecting to the globus pallidus. In order to gain insight into the neurochemical substrates of neuroleptic-induced c-fos expression, we examined the effects of adenosine A2 and N-methyl-D-aspartate (NMDA) receptor antagonists as well as inhibition of nitric oxide synthase, on haloperidol-induced Fos immunoreactivity in the striatum. While blockade of D1 receptors had no effect on haloperidol-induced Fos expression, adenosine A2 receptor antagonists decreased the number of neurons in the striatum expressing haloperidol-induced Fos by half. NMDA receptor antagonists also potently blocked the induction of Fos immunoreactivity by haloperidol, while inhibition of nitric oxide synthase activity had no effect. These results indicate that in the presence of a dopamine D2 antagonist, Fos expression in striato-pallidal neurons is mediated in part through activation of A2 receptors by adenosine, and via NMDA receptor activation by glutamate.
精神兴奋药物苯丙胺和可卡因通过激活 D1 多巴胺受体诱导纹状体中即早基因（如 c-fos）的表达。这主要发生在纹状体黑质神经元中。相反，抗精神病药物，如氟哌啶醇，可阻断 D2 型多巴胺受体，诱导投射到苍白球的纹状体神经元中 c-fos 的表达。为了深入了解抗精神病药物诱导 c-fos 表达的神经化学底物，我们研究了腺苷 A2 和 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂以及一氧化氮合酶抑制对氟哌啶醇诱导的纹状体 Fos 免疫反应性的影响。虽然阻断 D1 受体对氟哌啶醇诱导的 Fos 表达没有影响，但腺苷 A2 受体拮抗剂使纹状体中表达氟哌啶醇诱导 Fos 的神经元数量减少了一半。NMDA 受体拮抗剂也有力地阻断了氟哌啶醇诱导的 Fos 免疫反应性，而抑制一氧化氮合酶活性则没有影响。这些结果表明，在存在多巴胺 D2 拮抗剂的情况下，纹状体苍白球神经元中的 Fos 表达部分是通过腺苷激活 A2 受体以及谷氨酸激活 NMDA 受体介导的。
