Combining the α1 -adrenergic receptor antagonist, prazosin, with the ß-adrenergic receptor antagonist, propranolol, reduces alcohol drinking more effectively than either drug alone.

BACKGROUND: Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking α1 -adrenergic receptors with the antagonist, prazosin, decreased alcohol drinking in rats under various conditions. As noradrenergic activation is also regulated by ß-adrenergic receptors, we now examine the effects of the ß-adrenergic receptor antagonist, propranolol, alone or in combination with prazosin, on alcohol drinking in rats selectively bred for high voluntary alcohol intake and alcohol preference (P line). METHODS: Two studies were conducted with male P rats. In study 1, rats were allowed to become alcohol-dependent during 14 weeks of ad libitum access to food, water, and 20% alcohol, and the effect of propranolol (5 to 15 mg/kg, intraperitoneally [IP]) and prazosin (1 to 2 mg/kg, IP) on alcohol intake during withdrawal was assessed. In study 2, the effect of propranolol (5 mg/kg, IP) and prazosin (2 mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed. RESULTS: Alcohol drinking following propranolol treatment was variable, but the combination of propranolol + prazosin consistently suppressed alcohol drinking during both alcohol withdrawal and following prolonged imposed abstinence, and the combination of these 2 drugs was more effective than was treatment with either drug alone. CONCLUSIONS: Treatment with prazosin + propranolol, or a combination of other centrally active α1 - and ß-adrenergic receptor antagonists, may assist in preventing alcohol relapse in some individuals.