THE ROLE OF BRAIN 5‐HYDROXYTRYPTAMINE IN THE HYPERACTIVITY PRODUCED IN RATS BY LITHIUM AND MONOAMINE OXIDASE INHIBITION
Open Access
- 1 September 1974
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 52 (1), 19-26
- https://doi.org/10.1111/j.1476-5381.1974.tb09682.x
Abstract
1 Administration to rats of LiCl (3 mEq/kg) subcutaneously twice daily for 3 days followed by monoamine oxidase inhibition with either tranylcypromine (TCP; 20 mg/kg) or pargyline (75 mg/kg) on the fourth day produces a syndrome of hyperactivity indistinguishable from that produced by monoamine oxidase inhibition and l-tryptophan administration. 2 At least 3 injections of LiCl (3 mEq/kg) are necessary before hyperactivity is seen but one dose of LiCl (10 mEq/kg) 5 h before TCP also caused hyperactivity. The hyperactivity is blocked by prior administration of p-chlorophenylalanine, a tryptophan hydroxylase inhibitor. 3 LiCl pretreatment does not alter the concentration of l-tryptophan in the brain. However after monoamine oxidase inhibition the 5-hydroxytryptamine (5-HT) accumulation was significantly greater in animals given lithium indicating an increase in 5-HT synthesis of 70%. This was confirmed by measuring 5-hydroxyindoleacetic acid accumulation after probenecid (200 mg/kg). 4 The hyperactivity produced by the 5-HT analogue, 5-methoxy N,N-dimethyltryptamine was not potentiated by lithium pretreatment but one injection of LiCl (3 mEq/kg) which did not alter the rate of 5-HT synthesis, did potentiate the hyperactivity following TCP (20 mg/kg) and l-tryptophan (50 mg/kg). 5 These results suggest that lithium administration may cause an initial alteration of the 5-HT available for release at the nerve ending, which is followed after subsequent treatment by an increase in the rate of 5-HT synthesis. The possible clinical significance of these findings is discussed.Keywords
This publication has 20 references indexed in Scilit:
- THE PREVENTION BY INHIBITORS OF BRAIN PROTEIN SYNTHESIS OF THE HYPERACTIVITY AND HYPERPYREXIA PRODUCED IN RATS BY MONOAMINE OXIDASE INHIBITION AND THE ADMINISTRATION OF L‐TRYPTOPHAN OR 5‐METHOXY‐N,N‐DIMETHYLTRYPTAMINEJournal of Neurochemistry, 1972
- Relationship Between Serum Lithium Level and Clinical Response in Acute Mania Treated with LithiumThe British Journal of Psychiatry, 1972
- Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitorBritish Journal of Pharmacology, 1971
- PROPHYLACTIC LITHIUM IN AFFECTIVE DISORDERS: Controlled TrialThe Lancet, 1971
- STUDIES IN VIVO ON THE RELATIONSHIP BETWEEN BRAIN TRYPTOPHAN, BRAIN 5‐HT SYNTHESIS AND HYPERACTIVITY IN RATS TREATED WITH A MONOAMINE OXIDASE INHIBITOR AND L‐TRYPTOPHANJournal of Neurochemistry, 1971
- PROPHYLACTIC LITHIUM: DOUBLE BLIND DISCONTINUATION IN MANIC-DEPRESSIVE AND RECURRENT-DEPRESSIVE DISORDERSThe Lancet, 1970
- Lithium Prophylaxis in Recurrent Affective DisordersThe British Journal of Psychiatry, 1970
- Neuronally activated metabolism of brain serotonin: Effect of lithiumLife Sciences, 1970
- In Vivo Measurement of Brain Serotonin TurnoverPublished by Elsevier ,1968
- POTENTIATION OF THE ANTIDEPRESSIVE EFFECT OF A MONOAMINE-OXIDASE INHIBITOR BY TRYPTOPHANThe Lancet, 1963