Pj. Kenny et al., Evidence for a complex influence of nicotinic acetylcholine receptors on hippocampal serotonin release, J NEUROCHEM, 75(6), 2000, pp. 2409-2414
The effects of nicotine on 5-hydroxytryptamine (5-HT) release from serotone
rgic nerve endings in rat dorsal hippocampal slices were studied. Nicotine
(50-500 muM) caused a concentration-dependent increase in 5-HT release. Thi
s effect was antagonised by mecamylamine (0.5 muM), indicating an action at
nicotinic receptors. Nicotine-evoked 5-HT release was not affected by tetr
odotoxin (3 muM), cadmium chloride (0.1 mM), or the absence of Ca2+ or Nai
in the superfusion medium. Unexpectedly, higher concentrations of mecamylam
ine alone (1-50 muM) increased 5-HT release. This suggested the presence of
inhibitory input to 5-HT neurones and that these inhibitory neurones posse
ss tonically active nicotinic receptors. The effect of mecamylamine (50 muM
) on 5-HT release was reduced by the muscarinic M-1 receptor agonist, McN-A
-343 (100 muM), but pirenzepine(0.005-1 muM), which blocks M-1 receptors, a
lone increased 5-HT release. Hippocampal serotonergic neurones are known to
possess both excitatory nicotinic receptors and inhibitory M-1 receptors.
Although there may be several explanations for our results, one possible ex
planation is that nicotine stimulates 5-HT release by activating nicotinic
heteroreceptors on 5-HT terminals. Mecamylamine (0.5 muM) antagonises this
effect, but higher concentrations increase 5-HT release indirectly by block
ing the action of endogenous acetylcholine on nicotinic receptors situated
on cholinergic neurones that provide muscarinic inhibitory input to 5-HT ne
urones.