Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine

Abstract

Ponto-geniculo-occipital (PCO) waves induced either by the benzoquinolizine derivative, Ro 4-1284 (=PGO(CPA), were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in the preceding communication. The effect of various drugs interacting with central 5-hydroxytryptaminergic mechanisms on the density (number hr(-1) or number 0.5 hr(-1) of PGO waves was investigated. The density of PGO waves was dose-dependently decreased and the waves were eventually abolished by the precursors of 5-hydroxytryptamine (5-HT), L-tryptophan and 5-hydroxytryptophan. 5-HT itself, injected intracerebroventricularly, tended to diminish the density. Lysergic acid diethylamide (LSD) was an extremely potent depressor of PGO(1284) and PGO(PCPA); psilocybine was almost as potent as LSD, whereas higher doses of N,N-dimethyltryptamine, bufotenine and yohimbine were required for the reduction of PGO waves. A number of tricyclic antidepressants reduced the density of PGO waves, their order of potency corresponding to that reported for their inhibitory effect on the uptake of 5-HT; tertiary amines were more potent than secondary amines. Desipramine was more potent on PGO(PCPA) THAN ON PGO(1284). Two dibenzothiepine antipsychotics, methiothepin and octoclothepin, increased the density of PGO(1284) and PGO(PCPA) and also induced PGO waves in untreated cats; the evidence suggests that these two compounds antagonize the effect of endogenous 5-HT in the brain. These results confirm some earlier findings and augment the pharmacological pieces of evidence for the stron inhibitory influence of 5-HT neurones on the generation ofPGO waves.