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1 The effect of various f-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 P-Adrenoceptor antagonists that are not found in the brain in appreciable amount after peripheral injection, (±)-atenolol, (±)-practolol, (±)-labetalol and (±)-acebutalol, did not inhibit the 5-HTmediated behaviour.4 Neither the fl,-selective drug (±)-metoprolol, nor the 42-selective drug (±)-butoxamine inhibited the behavioural 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 ,B-adrenoceptor blocking drugs were inhibiting the post-synaptic 5-HTmediated 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 (PI and f2) adrenoceptor antagonists which have a high brain/ blood ratio following their peripheral injection, block 5-HT-mediated behavioural responses in the rat.

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Treatment of rats with one electroconvulsive shock (ECS) per day for 10 days enhanced the hyperactivity syndrome produced by administration of tranylcypromine (10 mg kg-1) and L-tryptophan (50 mg kg-1) given 24 h after the final shock. Similar enhancement was seen whether the shock was alternating sinusoidal or direct current (fractionated), whether it was given through unilaterally or bilaterally placed electrodes and whether or not a neuromuscular blocking agent (fazadinium) was used. Five shocks spread over 10 days or 8 shocks spread over 17 days were similarly effective, whilst 8 shocks in 1 day were ineffective. Therefore when ECS are given to rats in ways similar to those in which electroconvulsive therapy is given to patients with depression, enhancement of behavioural responses to increased 5-HT function is produced.

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