Central mechanisms of ethanol-induced adrenocortical response in selectively bred lines of mice.
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 alpha 2-adrenergic agonist, blocked ethanol-induced elevations in plasma corticosterone in a dose-dependent manner (1 and 10 micrograms) in LS mice; however, only the 10-micrograms 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 alpha 2-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 alpha-adrenergic antagonist, and propranolol, a beta-adrenergic antagonist at high doses (10 micrograms), produced slight increases in plasma corticosterone in LS mice only. Neither these compounds nor methoxamine, a nonspecific alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zgombick
J M
JM
Alcohol Research Center, School of Pharmacy, University of Colorado, Boulder.
Erwin
V G
VG
D000427:Alcohol Deterrents; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood* / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D008297:Male; D051379:Mice; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000427:Alcohol Deterrents; D015016:Yohimbine; D000431:Ethanol; D002217:Carbachol; D011433:Propranolol; D003000:Clonidine; D006221:Halothane; D003345:Corticosterone; D010646:Phentolamine