Abrahams T P, Liu W, Varner K J
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans, USA.
J Pharmacol Exp Ther. 1996 Nov;279(2):967-74.
The purpose of this study was to determine whether neurons in the rostral ventrolateral medulla play a role in the sympathoinhibitory response elicited by i.v. administration of cocaine and, if so, to identify the type(s) of receptors involved. Adrenergic antagonists were microinjected bilaterally into the rostral ventrolateral medulla in pentobarbital-anesthetized rats in an attempt to block the decrease in sympathetic nerve discharge (SND) elicited by cocaine (1 mg/kg i.v.). After the bilateral microinjection of saline, cocaine elicited a -56 +/- 5% (mean +/- S.E.) decrease in SND lasting 36 +/- 3 min. Cocaine also increased arterial pressure (21 +/- 3 mm Hg). Prior microinjection of the alpha-2 adrenergic antagonist idazoxan (0.3, 3 or 10 nmol) did not alter the magnitude of the sympathoinhibitory response to cocaine; however, the duration of the response was significantly reduced by all 3 doses (range 21 +/- 3 to 11 +/- 2 min). Similarly, microinjection of the alpha-2 adrenergic antagonist piperoxan (10 nmol) decreased the duration (from 45 +/- 8 to 23 +/- 4 min), but not the magnitude of the sympathoinhibitory response. Microinjection of either the alpha-1 adrenergic antagonist terazosin (0.24 nmol) or the beta adrenergic receptor antagonist propranolol (2 nmol) did not attenuate the decrease in SND elicited by cocaine. The cocaine-mediated pressor response was not affected by any of the antagonist treatments. These data show that the decrease in SND elicited by cocaine is mediated centrally and involves, at least in part, the activation of alpha-2 adrenergic receptors in the rostral ventrolateral medulla.
本研究的目的是确定延髓头端腹外侧区的神经元是否在静脉注射可卡因所引发的交感神经抑制反应中发挥作用，若发挥作用，则确定所涉及的受体类型。在戊巴比妥麻醉的大鼠中，将肾上腺素能拮抗剂双侧微量注射到延髓头端腹外侧区，以试图阻断可卡因（1毫克/千克静脉注射）引起的交感神经放电（SND）减少。双侧微量注射生理盐水后，可卡因使SND降低了-56±5%（平均值±标准误），持续36±3分钟。可卡因还使动脉血压升高（21±3毫米汞柱）。预先微量注射α-2肾上腺素能拮抗剂咪唑克生（0.3、3或10纳摩尔）并未改变对可卡因的交感神经抑制反应的幅度；然而，所有3个剂量均显著缩短了反应持续时间（范围为21±3至11±2分钟）。同样，微量注射α-2肾上腺素能拮抗剂哌罗克生（10纳摩尔）缩短了持续时间（从45±8分钟降至23±4分钟），但未改变交感神经抑制反应的幅度。微量注射α-1肾上腺素能拮抗剂特拉唑嗪（0.24纳摩尔）或β肾上腺素能受体拮抗剂普萘洛尔（2纳摩尔）均未减弱可卡因引起的SND降低。可卡因介导的升压反应不受任何拮抗剂处理的影响。这些数据表明，可卡因引起的SND降低是由中枢介导的，并且至少部分涉及延髓头端腹外侧区α-2肾上腺素能受体的激活。
