Contrasting effects of 5-hydroxytryptamine on the release of dopamine and acetylcholine in the nucleus accumbens of rat

Abstract

SummaryThe interaction between 5-hydroxytryptamine (5-HT) and the release of dopamine and acetylcholine in the nucleus accumbens of rat was investigated. 5-HT (20/~M) significantly decreased levels of [3H]-dopamine synthesized from [3H]-tyrosine. 5-HT also enhanced the release of [~4C]-dopamine at all concentrations of K + tested (up to 34 raM). The maximal effect of 5-HT occurred at 15 mM K + and was reversed by methysergide (3/zM). Increasing concentrations of Ca 2+ facilitated the releasing effect of 5-HT up to 1.2 mM Ca 2+. In contrast, 5-HT had an inhibitory effect on the K+-evoked release of [3H]-acetylcholine synthesized from [3H]-choline. 5-HT was not effective at non-depolarizing concentrations of K +. Increasing the external Ca 2+ concentration to 2.5 mM overcame the inhibition of [3H]-acetylcholine release due to 5-HT. These results indicate that 5-HT has at least two actions in the nucleus accumbens, one which is a methysergidesensitive facilitatory action on dopamine release promoted by Ca 2+ entry and a second, inhibitory effect on the K+-evoked release of acetylcholine, which is not blocked by methysergide and appears to operate by reducing Ca 2+ influx.

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

“…However, the effect is evident only at high doses of 5-HT (1OOumoll-) and is not changed even by a reuptake inhibitor such as paroxetine (Table 1). This pattern of action differs from that reported by other authors (De Belleroche & Gardiner, 1982;Gillet et al, 1985) who demonstrated that 5-HT even at low concentrations of 1-lOymol 1-1, inhibited tritium efflux induced by potassium (25 mmol -1) in rat brain slices. The different animal species (guinea-pig versus rat) and the different kind of stimulation (electrical stimulation vs KCl depolarization) are probably responsible for this discrepancy.…”

“…In fact, in the whole animal, 5-HT or 5-HT-mimetic drugs increase acetylcholine (ACh) content in different brain areas (Envrard et al, 1977;Samanin et al, 1978;Consolo et al, 1980), probably by inhibiting cholinergic neurone activity. Accordingly, 5-HT and 5-HTreleasing drugs reduce the ACh efflux from rat nucleus accumbens slices (De Belleroche & Gardiner, 1982) and from rat hippocampal synaptosomes (Maura & Raiteri, 1986).…”

Characterization of the effects of serotonin on the release of [3H]dopamine from rat nucleus accumbens and striatal slices

“…Evidence from many sources indicates that serotonergic input directly modulates nucleus accumbens and striatal neurons, but the level at which this interaction occurs is controversial. Studies on the release of DA have suggested that serotonin affects DA terminals in the nucleus accumbens and striatum (9)(10)(11)(12). In contrast, biochemical and behavioural studies have indicated that the effect of serotonin is post-synaptic to dopaminergic neurons in both the nucleus accumbens and striatum (13)(14)(15)(16).…”

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

“…For example, there is evidence that serotonin may inhibit (de Belleroche and Bradford 1980;Ennis et al 1981;Westfall and Tittermary 1982;Blandina et al 1988) as well as stimulate DA release in the striatum (Benloucif et al 1993;West and Galloway 1996;De Deurwaerdere et al 1997). Similarly, local application of 5-HT or 5-HT agonists have been shown to reduce (de Belleroche and Gardiner 1982) and facilitate dopamine efflux in the nucleus accumbens (Guan and McBride 1989;Parson and Justice 1993). In respect to the 5-HT 2 receptor agonist properties of psilocybin, it is of particular note that 3,4-methylenedioxymethamphetamine (MDMA), a potent 5-HT releasing agent, has been shown to increase impulse-mediated striatal dopamine release through 5-HT 2 receptor activation (Schmidt et al 1992;Palfreyman et al 1993;Schmidt et al 1994;Yamamoto et al 1995;Gudelsky and Nash 1996).…”