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 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.
Bianchi
C
C
Department of Pharmacology, University of Ferrera, Italy.
Ferraro
L
L
Tanganelli
S
S
Morari
M
M
Spalluto
G
G
Simonato
M
M
Beani
L
L
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018377:Neurotransmitter Agents; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D009538:Nicotine