Stevens K E, Fuller L L, Rose G M
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO.
Brain Res. 1991 Jul 26;555(1):91-8. doi: 10.1016/0006-8993(91)90864-r.
Dopaminergic and noradrenergic mediation of central sensory gating were assessed in Sprague-Dawley rats using a condition-test paradigm in which auditory evoked potentials were recorded. In this paradigm, unmedicated rats 'gate', i.e. suppress the response to the second of a pair of clicks delivered at a 0.5 s interval. Amphetamine-treated rats fail to gate; in this respect, they resemble schizophrenic humans. Previous studies had indicated noradrenergic involvement in the mediation of auditory gating in rats. In this study, we used selective antagonists to assess the contribution of alpha- and beta-adrenergic receptors, and dopamine D1- and D2-receptors, to amphetamine-induced alterations in gating. Both the alpha-antagonist, phentolamine, and the beta-antagonist, timolol, normalized gating by potentiating amphetamine-induced decreases in the amplitude of the test response. SCH 23390, a D1-receptor antagonist, also normalized gating, but by elevating the amphetamine-reduced amplitude of the conditioning response. Sulpiride did not significantly alter amphetamine-induced changes in gating. Thus, both noradrenergic alpha- and beta-receptors and dopamine D1-receptors appear to modulate gating. However, their dissimilar means of normalizing gating suggests that noradrenergic and dopaminergic drugs act via different mechanisms and possibly different neuroanatomical loci.
采用条件-测试范式，在斯普拉格-道利大鼠中评估多巴胺能和去甲肾上腺素能对中枢感觉门控的调节作用，其中记录听觉诱发电位。在该范式中，未用药的大鼠会“门控”，即抑制对以0.5秒间隔呈现的一对点击声中第二个点击声的反应。用苯丙胺处理的大鼠无法进行门控；在这方面，它们类似于精神分裂症患者。先前的研究表明，去甲肾上腺素能参与大鼠听觉门控的调节。在本研究中，我们使用选择性拮抗剂来评估α-和β-肾上腺素能受体以及多巴胺D1-和D2-受体对苯丙胺诱导的门控改变的作用。α-拮抗剂酚妥拉明和β-拮抗剂噻吗洛尔均通过增强苯丙胺诱导的测试反应幅度降低来使门控恢复正常。D1-受体拮抗剂SCH 23390也使门控恢复正常，但通过提高苯丙胺降低的条件反应幅度来实现。舒必利并未显著改变苯丙胺诱导的门控变化。因此，去甲肾上腺素能α-和β-受体以及多巴胺D1-受体似乎都对门控有调节作用。然而，它们使门控恢复正常的方式不同，这表明去甲肾上腺素能药物和多巴胺能药物通过不同的机制起作用，并且可能作用于不同的神经解剖位点。
