Effect of 5‐hydroxytryptamine on [³H]‐acetylcholine release from guinea‐pig striatal slices

Abstract

1 The effect of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked tritium efflux was studied in guinea-pig caudate nucleus slices preloaded with [3H]-choline. 2 5-HT, 10-300pmollP', temporarily increased the spontaneous tritium efflux (as well as the endogenous acetylcholine (ACh) release) and, after 15min perfusion, inhibited it. The facilitatory effect of 5-HT on spontaneous efflux was increased while the inhibitory effect did not occur in slices taken from dopamine-depleted guinea-pigs. 3 The increase in spontaneous tritium effiux by 5-HT was blocked by methiothepin, methysergide (pA2 8.7) and by the selective 5-HT2 antagonist, ritanserin (pA2 6.7).4 The inhibition of spontaneous tritium efflux by 5-HT was prevented by methysergide and methiothepin but not by ritanserin and (-)-propranolol. 5 5-HT, 100 pmol l-', inhibited the electrically-evoked tritium efflux and this effect was unchanged in dopamine-depleted slices.6 The inhibition of electrically-evoked tritium efflux by 5-HT was blocked by methiothepin and methysergide but not by (-)-propranolol or ritanserin. 7 These results suggest that 5-HT may exert a rapid and transient (excitatory) and a more prolonged (inhibitory) control over striatal cholinergic neurones.

Endogenous Serotonin Excites Striatal Cholinergic Interneurons via the Activation of 5-HT 2C, 5-HT6, and 5-HT7 Serotonin Receptors: Implications for Extrapyramidal Side Effects of Serotonin Reuptake Inhibitors

“…Thus, it might be postulated that the excitatory effect produced by 5-HT on cholinergic interneurons might represent, at least to some extent, a plausible determinant for the extrapyramidal side effects induced by 5-HT reuptake inhibitors, by promoting intrastriatal release of acetylcholine. This is in agreement with the evidence that 5-HT indeed stimulates acetylcholine release in the striatum (Bianchi et al, 1989). Hence, modulating striatal cholinergic signaling might prove useful to the pharmacological treatment of these movement disorders.…”

5-HT Receptor Regulation of Neurotransmitter Release

“…In guinea pig caudate nucleus slices, a 5-HT concentration as high as 100 M was necessary to produce an 18 to 20% inhibition of the electrically evoked [ 3 H]ACh release (Bianchi et al, 1989). This effect was inhibited by methiothepine and methysergide but not by ritanserin, a pattern of antagonist actions that would be compatible with the involvement of a receptor belonging to the 5-HT 1 family.…”

“…In guinea pig striatal slices, a stimulatory effect of 5-HT and DOI on ACh release mediated by 5-HT 2 receptors was also found, but this effect was abolished in the presence of 0.5 M tetrodotoxin, suggesting that the 5-HT 2 receptors are not located on the axon terminals of the cholinergic neurons but either on their somadendritic area or upstream on an interneuron within the slice (Bianchi et al, 1989;Siniscalchi et al, 1990).…”

“…1). In analogy to these results, it is probable that the same type of presynaptic 5-HT heteroreceptor on cholinergic nerves is also involved in the inhibition of electrically evoked [ 3 H]ACh release in slices of the rat hippocampus (Maura et al, 1989;Vizi and Kiss, 1998), guinea pig caudate nucleus (Bianchi et al, 1989), and human neocortex (Feuerstein and Seeger, 1997) as well as K ϩ -induced [ 3 H]ACh release in rat striatal slices (Gillet et al, 1985;Jackson et al, 1988). A decrease in electrically evoked [ 3 H]ACh release by the 5-HT receptor agonist CP-93129 (in the absence of TTX) was also observed (5-9 months after grafting) in hippocampal slices from rats that had undergone electrolytic or aspirative (Suhr et al, 1999) fimbria-fornix lesions and 2 weeks later had received intrahippocampal suspension grafts of fetal septal tissue.…”

5‐HT1A agonists increase and 5‐HT3 agonists decrease acetylcholine efflux from the cerebral cortex of freely‐moving guinea‐pigs

“…5-HT or 5-HT agonists increase acetylcholine (ACh) content in vivo and reduce ACh release from different brain areas in vitro (Envrard et al, 1977;Samanin et al, 1978;Consolo et al, 1980;Vizi et al, 1981;Gillet et al, 1985;Bianchi et al, 1989).…”