alpha1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol.
The purpose of this study was to test the hypothesis that blockade of alpha1-adrenergic receptors may suppress the excessive ethanol consumption associated with acute withdrawal in ethanol-dependent rats. Following the acquisition and stabilization of operant ethanol self-administration in male Wistar rats, dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14h/day. Subsequent to dependence induction, the effect of alpha1-noradrenergic receptor antagonist prazosin (0.0, 0.25, 0.5, 1, 1.5, and 2.0mg/kg IP) was tested on operant responding for ethanol in vapor-exposed and control rats during acute withdrawal. In ethanol-dependent animals, prazosin significantly suppressed responding at the 1.5 and 2.0mg/kg doses, whereas only the 2.0mg/kg dose was effective in nondependent animals, identifying an increase in the sensitivity to prazosin in dependent animals. Conversely, at the lowest dose tested (0.25mg/kg), prazosin increased responding in nondependent animals, which is consistent with the effect of anxiolytics on ethanol self-administration in nondependent animals. None of the doses tested reliably affected concurrent water self-administration. These results suggest the involvement of the noradrenergic system in the excessive alcohol drinking seen during acute withdrawal in ethanol-dependent rats.
Walker
Brendan M
BM
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA. bwalker@scripps.edu
Rasmussen
Dennis D
DD
Raskind
Murray A
MA
Koob
George F
GF
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000437:Alcoholism / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D012646:Self Administration
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D000431:Ethanol; D011224:Prazosin