Effects of β-adrenoceptor antagonists on alcohol drinking by alcohol-dependent rats.
BACKGROUND
Alcohol-dependent animals display enhanced stress responsivity, reward thresholds, and alcohol self-administration during alcohol withdrawal, and some of these aspects of alcohol dependence may be mediated by activation of brain norepinephrine (NE) systems.


OBJECTIVE
This study examined the effects of propranolol, a β-adrenoceptor antagonist, on operant alcohol-reinforced responding by alcohol-dependent and non-dependent rats.


METHODS
Adult male Wistar rats were trained to respond for alcohol in an operant conditioning paradigm on fixed-ratio-1 (FR-1) and progressive ratio (PR) reinforcement schedules. Rats were either made dependent on alcohol via chronic intermittent (14 h ON/10 h OFF) alcohol vapor inhalation or were not exposed to alcohol vapor. Rats were tested for the effects of propranolol (0-10 mg/kg) or nadolol (0-20 mg/kg) on operant alcohol-reinforced responding at the time point corresponding to 6-8 h withdrawal in dependent animals.


RESULTS
All doses of propranolol suppressed FR-1 operant alcohol-reinforced responding in alcohol-dependent rats, but only the highest dose suppressed FR-1 responding by controls. No dose of propranolol affected water responding. Nadolol did not affect operant behavior. Propranolol suppressed PR operant alcohol-reinforced responding across groups, an effect attributable to significant suppression of alcohol responding at the highest dose.


CONCLUSIONS
Following development of alcohol dependence, rats exhibit hypersensitivity to the suppressive effects of propranolol on operant alcohol-reinforced responding. This effect is mediated by central actions of the drug, is not attributable to motor effects, and may reflect activation of brain NE systems that contributes to withdrawal-induced negative emotional states and drives alcohol drinking in the dependent organism.
Gilpin
Nicholas W
NW
Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2400 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. nickg@scripps.edu
Koob
George F
GF
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000523:psychology; D000437:Alcoholism / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D009248:Nadolol / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D000431:Ethanol; D009248:Nadolol; D011433:Propranolol; D009638:Norepinephrine