Relationship between extracellular 5‐hydroxytryptamine and behaviour following monoamine oxidase inhibition and l‐tryptophan

Abstract

1 The present study investigates the effects of selective and a non-selective monoamine oxidase (MAO) inhibitors combined with l-tryptophan on MAO-A and -B activity, hypothalamic extracellular 5-hydroxytryptamine (5-HT) in vivo and the occurrence of the 5-HT behavioural syndrome. 2 Selective inhibition of intraneuronal MAO-A with MDL 72394 (0.5 mg kg⁻¹, i.p.) had no effect on extracellular 5-HT and following administration of L-tryptophan (50 mg kg⁻¹, i.p.) the 5-HT behavioural syndrome was not induced. 3 Selective inhibition of MAO-A at all sites with clorgyline (5 mg kg⁻¹, i.p.) increased extracellular 5-HT but did not induce the 5-HT behavioural syndrome when combined with l-tryptophan administration. 4 Selective inhibition of MAO-B with selegiline (10 mg kg⁻¹, i.p.) had no effect on extracellular 5-HT and the 5-HT behavioural syndrome was not observed after L-tryptophan administration. 5 Inhibition of MAO-A and -B with a higher and therefore non-selective, dose of MDL 72394 (2 mg kg⁻¹) markedly increased extracellular 5-HT but failed to induce the 5-HT behavioural syndrome after l-tryptophan administration. 6 Inhibition of MAO-A and -B at all sites in the brain (tranylcypromine 20 mg kg⁻¹, i.p. or clorgyline 5 mg kg⁻¹ plus selegiline 10 mg kg⁻¹) increased extracellular 5-HT and induced the behavioural syndrome on administration of l-tryptophan. 7 The results demonstrate that inhibition of MAO-A and -B both within amine neurones and elsewhere in the brain is essential for the development of the 5-HT behavioural syndrome. Whilst the syndrome is associated with increased extracellular 5-HT this does not appear necessarily to result in the syndrome and may indicate that increased extracellular 5-HT is not solely involved in the induction of the ‘5-HT behavioural syndrome’.