β-adrenergic antagonists attenuate withdrawal anxiety in cocaine-and morphine-dependent rats

Rats were treated chronically with either cocaine (20 mg/kg/day, 14 days), morphine (incrementing doses of 10 mg/kg/day to 80 mg/kg, 11 days) or saline. During morphine or cocaine abstinence (48 h), dependent rats showed increased anxiety-like behavior in a conditioned defensive burying paradigm as evidenced by significantly shorter latencies to begin burying as well as a 4-fold increase in burying duration relative to salinetreated animals. This withdrawal-induced increase in burying behavior was blocked by pretreatment with either the β-adrenergic antagonist propranolol (5 mg/kg) or the lipophobic selective β₁-antagonist, atenolol (5 mg/kg). These results are consistent with the possibility that activation of peripheral β₁ receptors may substantially contribute to withdrawal-induced anxiety and that β-adrenergic antagonists could be useful in treating in cocaine and morphine dependent addicts.