β‐ADRENOCEPTOR AGONISTS ENHANCE 5‐HYDROXYTRYPTAMINE‐MEDIATED BEHAVIOURAL RESPONSES

Abstract

The β‐adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5‐hydroxytryptamine‐mediated (5‐HT) hyperactivity. The lipophilic β‐adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind‐limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5‐HT agonist, 5‐methoxy N,N‐dimethyltryptamine (2 mg/kg) and the combination of tranylcypromine (10 mg/kg) and L‐tryptophan (50 mg/kg). Salbutamol and terbutaline potentiated quipazine‐induced hyperactivity only when given at the higher dose of 20 mg/kg. The effect of clenbuterol in enhancing quipazine hyperactivity was blocked by the centrally acting β1‐adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the β2‐adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting β1‐adrenoceptor antagonist, atenolol (5 mg/kg). Clenbuterol (5 mg/kg) did not enhance the circling responses produced by methamphetamine (0.5 mg/kg) in unilateral nigrostriatal‐lesioned rats. The results suggest that β‐adrenoceptor agonists in common with some established antidepressant treatments produce enhancement of 5‐HT‐mediated behavioural responses. 1982 British Pharmacological Society