Drugs and PGO waves in the lateral geniculate body of the curarized cat. IV. The effects of acetylcholine, GABA and benzodiazepines on PGO wave activity.

The possible involvement of cholinergic mechanisms and of GABA in the modulation and generation of ponto-geniculo-occipital (PGO) waves was studied using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 ( =PGO(1284)), and by p-chlorophenylalanine (=PGO(PCPA)), and continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats. Atropine had no significant effect on PGO(1284) but markedly depressed the density of PGO(PCPA) this effect of atropine was absent when the synthesis of noradrenaline (NA) was inhibited in addition to that of 5-hydroxytryptamine (5-HT). Arecoline and eserine at a low dose increased the density of PGO(PCPA). Both the stimulation of nicotinic receptors by nicotine and their blockade by mecamylamine reduced the amplitude of PGO(1284) and PGO(PCPA). Eserine, 0.3 mg kg(-1) i.v., had a similar effect. GABA injected into a lateral brain ventricle augmented the density of PGO(PCPA) but not the PGO(1284). Increasing the level of endogenous GABA by amino oxyacetic acid (AOAA) and by hydroxylamine affected PGO waves like GABA. Bicuculline tended to decrease the density of PGO(PCPA). Chlordiazepoxide increased the density of PGO(1284) and, more markedly, that of PGO(PCPA). The latter effect was prevented by atropine and by lesions placed in the amygdala, the septum and medial forebrain bundle several days prior to the acute experiment. It is concluded that synapse with nicotinic cholinergic receptors are prsent either in the neuronal network of the pontine reticular cells which trigger the PGO waves or within the pathway leading from this trigger area to the lateral geniculate body or within this structure. It is tentatively suggested that the noradrenergic neurones which depress the formaton of PGO waves, are under a modulating influence from limbic forebrain structures. The suggested pathway originating in the forebrain and projecting to the locus coeruleus seems to be inhibitory for the NA-neurones involved in the modulation of PGO waves and to contain muscarinic cholinergic and GABA-ergic synapse. Chlordiazepoxide might augment the density of PGO(PCPA) either by activating this pathway in the limbic forebrain or by enhancing GABA-ergic transmission at its ending.