Article date: October 1978
By: D.W. COSTAIN, A.R. GREEN in Volume 64, Issue 2, pages 193-200
The effect of various β‐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.
(±)‐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.
β‐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‐HT‐mediated behaviour.
Neither the β‐selective drug (±)‐metoprolol, nor the β2‐selective drug (±)‐butoxamine inhibited the behavioural response.
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‐dimethyltrypt‐amine, indicating that the β‐adrenoceptor blocking drugs were inhibiting the post‐synaptic 5‐HT‐mediated response.
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.
It is concluded that non‐selective (fix and p2) adrenoceptor antagonists which have a high brain/ blood ratio following their peripheral injection, block 5‐HT‐mediated behavioural responses in the rat.
The effect of various β‐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.
(±)‐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.
β‐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‐HT‐mediated behaviour.
Neither the β‐selective drug (±)‐metoprolol, nor the β2‐selective drug (±)‐butoxamine inhibited the behavioural response.
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‐dimethyltrypt‐amine, indicating that the β‐adrenoceptor blocking drugs were inhibiting the post‐synaptic 5‐HT‐mediated response.
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.
It is concluded that non‐selective (fix and p2) adrenoceptor antagonists which have a high brain/ blood ratio following their peripheral injection, block 5‐HT‐mediated behavioural responses in the rat.
DOI: 10.1111/j.1476-5381.1978.tb17289.x
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