Pharmacological studies on serotonin-mediated behaviour

1. Administration to rats of a monoamine oxidase inhibitor (for example tranylcypromine: Tcp) followed by L-tryptophan increases the rate of synthesis and release of 5-hydroxytryptamine (5-HT) and results in a series of behavioural changes, some of which can be recorded on activity meters or scored. Various putative 5-HT agonists and the releasing drugs, fenfluramine and p-chloroamphetamine, also produce these changes. 2. A supersensitive behavioural response was produced by specific lesioning or p-chlorophenylalanine pretreatment and lesioning and sectioning experiments suggested several of the behaviours to be either hind-brain or spinally mediated. 3. A role for dopamine and GABA in the behaviour was demonstrated, but depletion of brain noradrenaline by specific lesioning or administration of disulfiram did not influence the behavioural changes. 4. The behaviour produced by administration of Tcp/L-tryptophan or 5-methoxy N,N-dimethyl tryptamine was inhibited by the suggested 5-HT antagonists, methysergide, methergoline and (--)-propranolol, but not by cinanserin, mianserin and cyproheptadine, other putative antagonists. In contrast, all the antagonists inhibited the behaviour when it was produced by injection of the agonist, quipazine. 5. The possible reasons for these differences is discussed in the light of the receptor binding characteristics of the drugs and the possible existence of different 5-HT receptor populations.