Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines.

The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284). The stimulant of central alpha-adrenoceptors, clonidine, suppressed PGO(1284) and PGO(PCPA) in very small doses. Apomorphine in high doses had inconsistent depressant effects which were probably not related to its stimulant action on DA receptors. Release of brain NA by dexamphetamine and beta-tetrahydronaphthylamine decreased the density of PGO waves, alpha-Methyldopa diminished PGO(PCPA) but not PGO(1284. The MAO-inhibitor, nialamide, depressed PGO(PCPA) more than PCO(1284), whereas pheniprazine was inactive. The inhibitor of catechol-O-methyltransferase, tropolone, reduced the density of bially blocks the uptake of NA, was more potent on PGO(PCPA) than on PGO(1284). The alpha-adrenoceptor blocking agent, phenosybenzamine, markedly increased the density of PGO(PCPA). Similar effects were obtained with thioridazine and clozapine, which aare also known to be blockers of central alpha-adrenoceptors. Inhibition of tyrosine hydroxylase (by alpha-methyltyrosine) and of DA-beta-hydroxylase (by disulfiram or Ro 8-1981), in addition to the inhibition of tryptophan hydroxylase by PCPA, induced PGO waves comparable in density and temporal distribution to those occurring following the application of Ro 4-1284. The acute bilateral lesion of the dorsal and caudal parts of thel ocus coeruleus increased the density of PGO(PCPA). The results strongly suggest that, in addition to the 5-hydroxytryptaminergic system, noradrenergic neurones, probably originating in the locus coeruleus, depress the neurones in the pontine reticular formation involved in the generation of PGO waves.