5-HYDROXYTRYPTAMINE-MEDIATED EFFECTS OF NICOTINE ON ENDOGENOUS GABA EFFLUX FROM GUINEA-PIG CORTICAL SLICES

1 The effect of nicotine on endogenous basal GABA outflow was studied in guinea-pig cerebral cortex slices. 2 Nicotine 1.86-18.6 mu mol l(-1 ) significantly decreased the basal, tetrodotoxin-sensitive GABA efflu x, whereas at higher concentrations (186-620 mu mol l(-1)) nicotine in creased it. The inhibition was prevented by mecamylamine while the fac ilitation was blocked by mecamylamine, (+)-tubocurarine and tetrodotox in. 3 The effect of nicotine was due to an indirect 5-hydroxytryptamin ergic action. In fact, MDL 72222 (1 mu mol l(-1)) completely prevented the alkaloid inhibition and methysergide (l mu mol l(-1)) reversed th e facilitation into inhibition; concomitant treatment with methysergid e and MDL 72222 antagonized the effect of nicotine at 186 mu mol l(-1) 4 Lower concentrations of 5-HT (3-10 mu mol l(-1)) decreased, whereas higher concentrations (30-100 mu mol l(-1)) increased, spontaneous GA BA outflow. The inhibition of GABA efflux was prevented by MDL 72222 w hereas the facilitation was reversed by methysergide (1 mu mol l(-1)) into inhibition, and prevented by MDL72222 1 mu mol l(-1). 5 These res ults suggest that, by activating nicotinic receptors present on 5-hydr oxytryptaminergic terminals, nicotine releases 5-HT which, in turn, in hibits or increases the secretory activity of cortical GABA interneuro nes via 5-HT, and methysergide-sensitive receptors, respectively.