Abrahams T P, Varner K J
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112, USA.
Physiol Behav. 1998 Feb 15;63(4):629-34. doi: 10.1016/s0031-9384(97)00510-6.
Cocaine increases the circulating levels of plasma catecholamines, presumably via the activation of the sympathoadrenal axis. However, a number of reports have shown that the predominant response to cocaine is a generalized decrease in sympathetic nerve activity. One possible explanation for the increase in plasma catecholamines may be that the adrenal sympathetic nerve is less sensitive to the sympathoinhibitory actions of cocaine than are other nerves. This study compared the effects of cocaine on adrenal and renal sympathetic nerve discharge (SND) recorded simultaneously in pentobarbital-anesthetized rats. Cocaine produced dose-related decreases in both renal and adrenal SND; however, the decreases in adrenal SND were significantly smaller than in renal SND. Cocaine also elicited pressor responses in these rats. The decreases in adrenal SND were similar in baroreceptor intact and sinoaortically denervated rats, indicating that pressor-mediated baroreceptor reflex activation was not responsible for the decrease in adrenal SND. In a separate group of rats, i.v. administration of desipramine decreased both adrenal and renal SND. As with cocaine, the decreases in adrenal SND after desipramine were smaller, suggesting that the differences in the neural responses did not reflect a differential local anesthetic effect of cocaine on the two nerves. In conclusion, these studies showed that cocaine decreases adrenal SND in pentobarbital-anesthetized rats. However, the adrenal sympathetic nerve is less sensitive than the renal nerve to the sympathoinhibitory actions of cocaine. Whether the adrenal SND remaining after cocaine contributes to the increase in plasma catecholamines produced by this drug remains to be determined.
可卡因可能通过激活交感 - 肾上腺轴来提高血浆儿茶酚胺的循环水平。然而，许多报告表明，对可卡因的主要反应是交感神经活动普遍下降。血浆儿茶酚胺增加的一个可能解释是，肾上腺交感神经对可卡因的交感抑制作用比其他神经更不敏感。本研究比较了可卡因对戊巴比妥麻醉大鼠同时记录的肾上腺和肾交感神经放电（SND）的影响。可卡因使肾和肾上腺SND均出现剂量相关的下降；然而，肾上腺SND的下降明显小于肾SND的下降。可卡因还在这些大鼠中引起升压反应。在压力感受器完整和去窦主动脉神经支配的大鼠中，肾上腺SND的下降相似，表明压力介导的压力感受器反射激活不是肾上腺SND下降的原因。在另一组大鼠中，静脉注射地昔帕明可降低肾上腺和肾SND。与可卡因一样，地昔帕明后肾上腺SND的下降较小，这表明神经反应的差异并不反映可卡因对这两条神经的局部麻醉作用不同。总之，这些研究表明，可卡因可降低戊巴比妥麻醉大鼠的肾上腺SND。然而，肾上腺交感神经对可卡因的交感抑制作用比肾神经更不敏感。可卡因后残留的肾上腺SND是否导致该药物引起的血浆儿茶酚胺增加仍有待确定。
