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. 1995 Nov;116(6):2724–2728. doi: 10.1111/j.1476-5381.1995.tb17233.x

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

C Bianchi 1, L Ferraro 1, S Tanganelli 1, M Morari 1, G Spalluto 1, M Simonato 1, L Beani 1
PMCID: PMC1909134  PMID: 8590996

Abstract

1. The effect of nicotine on endogenous basal GABA outflow was studied in guinea-pig cerebral cortex slices. 2. Nicotine 1.86-18.6 mumol l-1 significantly decreased the basal, tetrodotoxin-sensitive GABA efflux, whereas at higher concentrations (186-620 mumol l-1) nicotine increased it. The inhibition was prevented by mecamylamine while the facilitation was blocked by mecamylamine, (+)-tubocurarine and tetrodotoxin. 3. The effect of nicotine was due to an indirect 5-hydroxytryptaminergic action. In fact, MDL 72222 (1 mumol l-1) completely prevented the alkaloid inhibition and methysergide (1 mumol l-1) reversed the facilitation into inhibition; concomitant treatment with methysergide and MDL 72222 antagonized the effect of nicotine at 186 mumol l-1 4. Lower concentrations of 5-HT (3-10 mumol l-1) decreased, whereas higher concentrations (30-100 mumol l-1) increased, spontaneous GABA outflow. The inhibition of GABA efflux was prevented by MDL 72222 whereas the facilitation was reversed by methysergide (1 mumol l-1) into inhibition, and prevented by MDL 72222 1 mumol l-11. 5. 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.

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Selected References

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