The role of brain 5-hydroxytryptamine in the hyperactivity produced in rats by lithium and monoamine oxidase inhibition.
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 potentiaed 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.
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002027:Bufotenin / Q000032:analysis / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D013268:Stimulation, Chemical; D014191:Tranylcypromine / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D002027:Bufotenin; D012701:Serotonin; D014191:Tranylcypromine; D014364:Tryptophan; D008094:Lithium; D010293:Pargyline; D010134:Fenclonine