Ruskin D N, Marshall J F
Department of Psychobiology, University of California, Irvine 92717.
Synapse. 1994 Nov;18(3):233-40. doi: 10.1002/syn.890180309.
Amphetamine or cocaine injection causes expression of the immediate-early gene c-fos in the striatum. Previous studies have shown that dopamine D1 receptor activation is necessary for this effect, but have not established a consistent role for D2 receptors. We have investigated the involvement of D2 receptors in indirect dopamine agonist-induced striatal Fos-like immunoreactivity using the selective D2 antagonist eticlopride. Eticlopride treatment (0.5 mg/kg) caused Fos expression by itself, but also decreased Fos expression in the central striatum due to amphetamine (5.0 mg/kg) or cocaine (40 mg/kg) by 90% and 85%, respectively. In striatonigral neurons, identified by labeling with the retrograde tracer Fluorogold iontophoresed into the substantia nigra pars reticulata, the blockade of stimulant-induced Fos-like immunofluorescence by eticlopride was nearly complete, with decreases of 98% for amphetamine and 94% for cocaine. In striatonigral neurons, the D2 antagonist alone had minimal effect. We conclude that activation of both D1 and D2 receptor classes by dopamine agonists is necessary for induction of Fos in the striatonigral cells of normal rats. These results provide an important parallel to behavioral and electrophysiological work that also demonstrates D1/D2 interdependence in the control of normal basal ganglia functions.
注射苯丙胺或可卡因会导致纹状体中即早基因c-fos的表达。先前的研究表明，多巴胺D1受体的激活对于这种效应是必要的，但尚未确定D2受体的一致作用。我们使用选择性D2拮抗剂依托必利，研究了D2受体在间接多巴胺激动剂诱导的纹状体Fos样免疫反应中的作用。依托必利治疗（0.5mg/kg）本身会导致Fos表达，但同时也会使苯丙胺（5.0mg/kg）或可卡因（40mg/kg）诱导的纹状体中央Fos表达分别降低90%和85%。在用逆行示踪剂氟金离子电渗到黑质网状部进行标记所鉴定的纹状体黑质神经元中，依托必利对兴奋剂诱导的Fos样免疫荧光的阻断几乎是完全的，苯丙胺和可卡因分别降低了98%和94%。在纹状体黑质神经元中，单独使用D2拮抗剂的作用最小。我们得出结论，多巴胺激动剂激活D1和D2受体类别对于正常大鼠纹状体黑质细胞中Fos的诱导都是必要的。这些结果与行为学和电生理学研究结果形成重要平行，后者也证明了在正常基底神经节功能控制中D1/D2的相互依赖性。
