ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The effects of nicotine on 5-hydroxytryptamine (5-HT)release from serotonergic nerve endings in rat dorsal hippocampal slices werestudied. Nicotine (50-500 μM) caused a concentration-dependentincrease in 5-HT release. This effect was antagonised by mecamylamine (0.5μM), indicating an action at nicotinic receptors. Nicotine-evoked5-HT release was not affected by tetrodotoxin (3 μM), cadmiumchloride (0.1 mM), or the absence of Ca2+ orNa+ in the superfusion medium. Unexpectedly, higher concentrationsof mecamylamine alone (1-50 μM) increased 5-HT release. Thissuggested the presence of inhibitory input to 5-HT neurones and that theseinhibitory neurones possess tonically active nicotinic receptors. The effectof mecamylamine (50 μM) on 5-HT release was reduced by themuscarinic M1 receptor agonist, McN-A-343 (100 μM), butpirenzepine (0.005-1 μM), which blocks M1 receptors,alone increased 5-HT release. Hippocampal serotonergic neurones are known topossess both excitatory nicotinic receptors and inhibitory M1receptors. Although there may be several explanations for our results, onepossible explanation is that nicotine stimulates 5-HT release by activatingnicotinic heteroreceptors on 5-HT terminals. Mecamylamine (0.5 μM)antagonises this effect, but higher concentrations increase 5-HT releaseindirectly by blocking the action of endogenous acetylcholine on nicotinicreceptors situated on cholinergic neurones that provide muscarinic inhibitoryinput to 5-HT neurones.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0752409.x
