5‐Hydroxytryptamine‐mediated effects of nicotine on endogenous GABA efflux from guinea‐pig cortical slices
Open Access
- 1 November 1995
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 116 (6) , 2724-2728
- https://doi.org/10.1111/j.1476-5381.1995.tb17233.x
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 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. 3 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 4 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. 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.Keywords
This publication has 29 references indexed in Scilit:
- Stimulation by nicotine of the spontaneous release of [3H]γ-aminobutyric acid in the substantia nigra and in the globus pallidus of the ratBrain Research, 1994
- Systemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental areaSynapse, 1994
- Effects of systemic nicotine on serotonin release in rat brainBrain Research, 1993
- Effect of nicotine on levels of extracellular amino acids in regions of the rat brain in vivoNeuropharmacology, 1993
- Inhibition of [3H] γ‐aminobutyric acid release from guinea‐pig hippocampal synaptosomes by serotonergic agentsFundamental & Clinical Pharmacology, 1992
- Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brainActa Physiologica Scandinavica, 1991
- Nicotine-induced inhibition of cerebellar purkinje neurons: Specific actions of nicotine and selective blockade by mecamylamineNeuropharmacology, 1989
- A Search for Receptors Modulating the Release of γ‐[3H]Aminobutyric Acid in Rabbit Caudate Nucleus SlicesJournal of Neurochemistry, 1986
- Release of dopamine and 5-hydroxytryptamine from rat striatal slices following activation of nicotinic cholinergic receptorsGeneral Pharmacology: The Vascular System, 1983
- The effects of nicotine on brain neurotransmitter systemsPharmacology & Therapeutics, 1982