Rationale: 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.
Objectives: 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.