5-Hydroxytryptamine-mediated effects of nicotine on endogenous GABA efflux from guinea-pig cortical slices

The effect of nicotine on endogenous basal GABA outflow was studied in guinea‐pig cerebral cortex slices. Nicotine 1.86‐18.6 μmol 1−1 significantly decreased the basal, tetrodotoxin‐sensitive GABA efflux, whereas at higher concentrations (186–620 μmol 1−1) nicotine increased it. The inhibition was prevented by mecamylamine while the facilitation was blocked by mecamylamine, (+)‐tubocurarine and tetrodotoxin. The effect of nicotine was due to an indirect 5‐hydroxytryptaminergic action. In fact, MDL 72222 (1 μmol 1−1) completely prevented the alkaloid inhibition and methysergide (1 μmol 11) reversed the facilitation into inhibition; concomitant treatment with methysergide and MDL 72222 antagonized the effect of nicotine at 186 μmol 1−1 Lower concentrations of 5‐HT (3–10 μmol 1−1) decreased, whereas higher concentrations (30–100 μmol 1−1) increased, spontaneous GABA outflow. The inhibition of GABA efflux was prevented by MDL 72222 whereas the facilitation was reversed by methysergide (1 μmol 1−1) into inhibition, and prevented by MDL 72222 1 μmol 1−11. These results suggest that, by activating nicotinic receptors present on 5‐hydroxytryptaminergic terminals, nicotine releases 5‐HT which, in turn, inhibits or increases the secretory activity of cortical GABA interneurones via 5‐HT3 and methysergide‐sensitive receptors, respectively. 1995 British Pharmacological Society