Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses.
Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses.
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莫索尼定在轻度低血压剂量下诱导的非肾上腺素能探索行为。
DOI：
10.1016/s0006-8993(02)03754-x
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发表时间：
2003
期刊：
影响因子：
2.9
通讯作者：
Piletz,JohnE
中科院分区：
文献类型：
--
作者：
Zhu,He;Paul,IanA;Stec,DavidE;Peeler,DudleyF;Piletz,JohnE
莫索尼定是一种具有中心活性的咪唑啉类化合物，它与咪唑啉受体(IR)的亲和力高于α2肾上腺素受体(α2AR)。在临床上，由于莫索尼定镇静副作用的发生率较低，已被证明比单纯的α2-肾上腺素能激动剂(即呋喃苯肼)更有利于治疗高血压。本实验揭示了小剂量莫索尼定和异烟肼对C57BL/6小鼠探索性行为的不同影响。小剂量莫索尼定(0.0 5 mg·kg-1·−，ip)与生理盐水注射对照组相比，与生理盐水注射对照组相比，新对象接触增加(+36%)，更多的运动进入中央空间(+56%；P<；0.01)；而在相同的范例中，吧那苯只诱导剂量响应性镇静药样行为。然而，这两种激动剂在相似的剂量范围内(0.025-0.1mgkg−1i.p)在血压变化方面没有区别。在有意识自由活动的小鼠中(莫索尼定的Δ平均值±S.E.M.=−12.3±3.2 mm Hg，而愈创木酚的−为13.5±1.9 mm Hg)。如预期的那样，α-2AR参与的镇静作用可被非咪唑啉α-2AR拮抗剂SKF86466(0.5或1.0 mg·kg-1·−，ip)完全阻断。但SKF86466不能拮抗小剂量莫索尼定(0.0 5或0.1 mg kg−1)的促探效应。这些结果表明，莫索尼定优先通过非肾上腺素能机制发挥作用，可能是IR介导的，以诱导前探索性行为。
Moxonidine is a centrally-active imidazoline compound with preferential affinity for imidazoline receptors (IR) over α2-adrenoceptors (α2AR). Clinically, moxonidine has proven advantageous for treating hypertension over pure α2-adrenergic agonists (i.e., guanabenz) due to its lowered incidence of sedative side effects. The present experiments reveal divergent behavioral effects of low doses of moxonidine and guanabenz in C57Bl/6 mice in an exploratory arena. Low-dose moxonidine (0.05 mg kg−1i.p.) elicited an increase in novel object contacts (+36%) and more movement into central space (+56%; P<0.01) compared to saline-injected controls; whereas guanabenz induced only dose-responsive sedative-like behaviors in the same paradigm. Yet, the two agonists were indistinguishable in terms of blood pressure changes over a similar dose range (0.025–0.1 mg kg−1i.p.) in consciously free-moving mice (Δ mean±S.E.M.=−12.3±3.2 mm Hg for moxonidine versus −13.5±1.9 mm Hg for guanabenz). As expected of α2AR involvement, the sedative-like effects of guanabenz were completely blocked by pretreatment with the non-imidazoline α2AR-antagonist, SKF86466 (0.5 or 1.0 mg kg−1i.p.). However, the pro-exploratory effects of low doses of moxonidine (0.05 or 0.1 mg kg−1) were not antagonized by SKF86466. These results suggest that moxonidine acts preferentially through a non-adrenergic mechanism, possibly IR-mediated, to elicit pro-exploratory behavior.
莫索尼定和认知功能：与吗氯贝胺和劳拉西泮的相互作用
影响因子：
2.9
作者：
K. Wesnes;Pippa M. Simpson;B. Jansson;A. Grahnén;H. Weimann;H. Küppers
通讯作者：
H. Küppers