THE EFFECTS OF PUTATIVE 5‐HYDROXYTRYPTAMINE ANTAGONISTS ON THE BEHAVIOUR PRODUCED BY ADMINISTRATION OF TRANYLCYPROMINE AND L‐TRYPTOPHAN OR TRANYLCYPROMINE AND L‐DOPA TO RATS

1 The putative 5‐hydroxytryptamine (5‐HT) receptor blocking drugs methysergide (10 mg/kg) and methergoline (5 mg/kg) were found to abolish some components of the hyperactivity syndrome, including head weaving and forepaw treading, which follow administration to rats of tranylcypromine (20 mg/kg) and L‐tryptophan (100 mg/kg). Hyperactivity and hyper‐reactivity were potentiated with a resultant increase in automated locomotor activity counts. In contrast (—)‐propranolol (20 mg/kg) inhibited all features of the syndrome. The same results were obtained with these drugs when the behaviour was elicited by p ‐chloroamphetamine (10 mg/kg) or by tranylcypromine and tryptamine (10 mg/kg). 2 Methysergide and methergoline had similar effects on the syndrome produced by tranylcypromine and l‐ DOPA (50 mg/kg) whereas propranolol was without effect. 3 None of the putative 5‐HT receptor antagonists affected brain 5‐HT turnover as assessed by rate of accumulation of 5‐HT following monoamine oxidase inhibition with tranylcypromine. 4 Microinjections of 5,7‐dihydroxytryptamine into the spinal cord resulted in a 70% fall in cord 5‐HT concentrations without an effect on brain 5‐HT concentrations. The behavioural response to the putative 5‐HT receptor agonist, 5‐methoxy JV, N‐dimethyltryptamine (2 mg/kg), was potentiated in these animals suggesting that 5‐HT receptors become supersensitive on denervation, and that some components of the behavioural syndrome are mediated by spinal cord 5‐HT receptors. 5 Pretreatment with α‐methyl p‐tyrosine (2 × 200 mg/kg) delayed the onset of all components of the behaviour elicited by tranylcypromine/L‐tryptophan by 60 min, indicating an involvement of catecholamines in the syndrome. 6 p‐Chloroamphetamine‐induced 5‐HT depletion had no effect on any component of the tranylcypromine‐L‐DOPA behaviour.