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Relationship between extracellular 5‐hydroxytryptamine and behaviour following monoamine oxidase inhibition and l ‐tryptophan
Author(s) -
Sleight A.J.,
Marsden C.A.,
Martin K.F.,
Palfreyman M.G.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11435.x
Subject(s) - extracellular , tranylcypromine , clorgyline , monoamine oxidase b , monoamine oxidase , selegiline , pharmacology , chemistry , monoamine neurotransmitter , serotonin , tryptophan , monoamine oxidase a , tryptophan hydroxylase , monoamine oxidase inhibitor , endocrinology , medicine , biochemistry , biology , serotonergic , enzyme , amino acid , receptor , disease , parkinson's disease
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’.