beta-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine

Abstract

1 The effect of various beta-adrenoceptor blocking agents on the 5-hydroxytryptamine (5-HT)-induced hyperactivity response produced in rats by administration of tranylcypromine (10 mg/kg i.p.) followed by L-tryptophan (50 mg/kg i.p.) has been investigated. 2 (+/-)-Alprenolol, (+/-)-timolol, (+/-)-sotalol, (+/-)-pindolol (all at 40 mg/kg) all inhibited the hyperactivity response to some degree when given 45 min before the tranylcypromine, as did (+/-)-oxprenolol when given after the L-tryptophan. 3 beta-Adrenoceptor antagonists that are not found in the brain appreciable amount after peripheral injection, (+/-)-atenolol, (+/-)-practolol, (+/-)-labetalol and (+/-)-acebutalol, did not inhibit the 5-HT-mediated behaviour. 4 Neither the beta1-selective drug (+/-)-metoprolol, nor the beta2-selective drug (+/-)-butoxamine inhibited the behavioral response. 5 The drugs that blocked the 5-HT-mediated behaviour did not alter brain 5-HT concentrations, synthesis rate or the accumulation of 5-HT following tranylcypromine/L-tryptophan. However, they did inhibit the hyperactivity produced by the suggested 5-HT agonist, 5-methoxy N,N-dimethyltryptamine, indicating that the beta-adrenoceptor blocking drugs were inhibiting the post-synaptic 5-HT-mediated response. 6 Circling produced by methamphetamine (3 mg/kg) in unilateral nigro-striatal lesioned rats was not altered by alprenolol, sotalol, pindolol or metaprolol, indicating that these drugs do not alter dopamine-mediated behaviour. 7 It is concluded that non-selective (beta1 and beta2) adrenoceptor antagonists which have a high brain/blood ratio following their peripheral injection, block 5-HT-mediated behavioural responses in the rat.