Martin G E, Papp N L
Pharmacol Biochem Behav. 1984 Jun;20(6):893-7. doi: 10.1016/0091-3057(84)90014-5.
Previously the ipsiversive turning response elicited by MK-801 in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra has been shown to be reduced by the alpha 1-receptor antagonist, prazosin. In these experiments the effects of additional alpha 1-adrenoceptor antagonists were examined to verify the involvement of alpha 1-adrenoceptors in the elucidation of the ipsiversive turning response elicited by MK-801. Both aceperone and azapetine did significantly reduce the ipsiversive turning evoked by MK-801. In contrast, neither agent produced a statistically significant reduction in the contraversive turning evoked by the direct acting dopamine agonist, apomorphine. In addition, aceperone also produced a weak but dose-related inhibition of amphetamine-induced ipsiversive rotation, whereas azapetine partially reduced amphetamine-induced turning a non-dose related manner. These data suggest alpha 1-adrenoceptors may be partially involved in the ipsiversive turning response caused by MK-801 and to a lesser extent by amphetamine. This theory was further supported by the finding that reduction of endogenous norepinephrine levels, via administration of the dopamine-beta-hydroxylase inhibitor FLA-63, markedly reduced the turning evoked by MK-801 and to a lesser degree that produced by amphetamine.
先前已表明，在单侧黑质6-羟基多巴胺损伤的大鼠中，MK-801引发的向患侧旋转反应会被α1受体拮抗剂哌唑嗪减弱。在这些实验中，研究了其他α1肾上腺素能受体拮抗剂的作用，以验证α1肾上腺素能受体在阐明MK-801引发的向患侧旋转反应中的参与情况。阿塞哌隆和阿扎哌丁均能显著减少MK-801诱发的向患侧旋转。相比之下，这两种药物对直接作用的多巴胺激动剂阿扑吗啡诱发的向对侧旋转均未产生统计学上的显著降低作用。此外，阿塞哌隆还对苯丙胺诱导的向患侧旋转产生了微弱但与剂量相关的抑制作用，而阿扎哌丁则以非剂量相关的方式部分降低了苯丙胺诱导的旋转。这些数据表明，α1肾上腺素能受体可能部分参与了由MK-801引起的向患侧旋转反应，在较小程度上也参与了由苯丙胺引起的反应。通过给予多巴胺-β-羟化酶抑制剂FLA-63来降低内源性去甲肾上腺素水平，这一发现显著降低了MK-801诱发的旋转，并在较小程度上降低了苯丙胺诱发的旋转，进一步支持了这一理论。
