β‐ADRENOCEPTOR AGONISTS ENHANCE 5‐HYDROXYTRYPTAMINE‐MEDIATED BEHAVIOURAL RESPONSES
COWEN PJ., GRAHAME SMITH DG., GREEN AR., HEAL DJ.
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 β 1 ‐adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the β 2 ‐adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting β 1 ‐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