Central mechanisms of ethanol-induced adrenocortical response in selectively bred lines of mice.
Central mechanisms of ethanol-induced adrenocortical response in selectively bred lines of mice.
复制标题
选择性繁殖的小鼠系中乙醇诱导的肾上腺皮质反应的中心机制。
DOI：
10.1159/000124840
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发表时间：
1987
影响因子：
4.1
通讯作者：
Erwin,VG
中科院分区：
文献类型：
--
作者：
Zgombick,JM;Erwin,VG
选择性繁殖的长睡眠(LS)和短睡眠(SS)小鼠在乙醇诱导的肾上腺皮质反应方面存在显著差异。在两个品系的小鼠中，脑室注射生理盐水都能引起‘应激诱导’的肾上腺皮质反应，而脑室内注射去甲肾上腺素和胆碱能化合物则不同地调节乙醇诱导的和应激诱导的肾上腺皮质反应。α2-肾上腺素能激动剂可乐定以剂量依赖的方式(1和10微克)阻断乙醇诱导的LS小鼠血浆皮质酮的升高；然而，只有10微克剂量的可乐定能有效地拮抗SS小鼠的这一反应。可乐定对应激诱导的肾上腺皮质活动的阻断作用不如乙醇诱导的。α2-肾上腺素能拮抗剂育亨宾可使LS小鼠血浆皮质酮显著升高，但对SS小鼠无明显影响；但该化合物不改变乙醇诱导的两种小鼠的肾上腺皮质反应。育亨宾逆转可乐定对乙醇诱导的LS和SS小鼠的抑制作用。非特异性α肾上腺素能拮抗剂酚妥拉明和高剂量(10微克)β肾上腺素能拮抗剂普萘洛尔仅使LS小鼠血浆皮质酮略有升高。这些化合物和甲氧胺(一种非特异性α肾上腺素能激动剂)都不能改变乙醇对LS或SS小鼠肾上腺皮质活动的影响。卡巴胆碱是一种混合的毒碱/尼古丁激动剂，可显著增加LS和SS小鼠的肾上腺皮质反应，并增强乙醇诱导的两种小鼠血浆皮质酮的升高。然而，非特异性M受体拮抗剂阿托品或烟碱受体拮抗剂六甲溴铵不能改变乙醇诱导的LS和SS小鼠血浆皮质酮的升高。这些结果表明，乙醇引起的肾上腺皮质激活可能主要是通过中枢去甲肾上腺素能系统介导的，这些系统的差异可能是乙醇引起LS和SS小鼠血浆皮质酮升高的不同原因。
Selectively bred long-sleep (LS) and short-sleep (SS) mice differ markedly in ethanol-induced adrenocortical response. Intracerebroventricular injections of saline elicited a ‘stress-induced’ adrenocortical response in both lines of mice, and intracerebroventricular infusions of noradrenergic and cholinergic compounds modulated ethanol-induced and stress-induced adrenocortical responses differentially in these mice. Clonidine, an α2-adrenergic agonist, blocked ethanol-induced elevations in plasma corticosterone in a dose-dependent manner (1 and 10 µg) in LS mice; however, only the 10-µg dose of clonidine effectively antagonized this response in SS mice. Clonidine was less effective in blocking adrenocortical activity induced by stress than that induced by ethanol. Yohimbine, an α2-adrenergic antagonist, induced a marked elevation in plasma corticosterone in LS mice but not in SS mice; however, this compound did not alter ethanol-induced adrenocortical responses in either line of mice. Yohimbine reversed the inhibitory effect of clonidine in ethanol-treated LS and SS mice. Phentolamine, a nonspecific α-adrenergic antagonist, and propranolol, a β-adrenergic antagonist at high doses (10 µg), produced slight increases in plasma corticosterone in LS mice only. Neither these compounds nor methoxamine, a nonspecific α-adrenergic agonist, altered the effect of ethanol on adrenocortical activity in LS or SS mice. Carbachol, a mixed muscarinic/nicotinic agonist, significantly increased adrenocortical response in both LS and SS mice and potentiated ethanol-induced elevation in plasma corticosterone in both lines of mice. However, atropine, a nonspecific muscarinic antagonist, or hexamethonium, a nicotinic antagonist, did not modify ethanol-induced elevations in plasma corticosterone in LS and SS mice. These results suggest that adrenocortical activation produced by ethanol may be mediated primarily through central noradrenergic systems and that differences in these systems may account for the differential ethanol-induced elevation in plasma corticosterone exhibited by LS and SS mice.