Extracellular 5-hydroxytryptamine inhibits 5-hydroxytryptamine release from rat brain cortex slices

Abstract

Rat brain cortex slices preincubated with 3H-5-hydroxytryptamine were superfused with physiological salt solution and stimulated electrically, or they were superfused with Ca2+-free solution containing 25 mM K+ and stimulated by introduction of 1.3 mM CaCl2 for 2 min. After blockade of neuronal 5-hydroxy-tryptamine (5-HT) uptake with clomipramine or paroxetine, the 3H overflow evoked by both methods of stimulation was decreased by unlabelled 5-HT and increased by methiothepin. The inhibition caused by 5-HT was antagonized by simultaneous administration of methiothepin. The inhibition by 5-HT of Ca2+-induced overflow was also observed in the presence of tetrodotoxin. These results suggest that 5-HT regulates its own release from central serotoninergic neurones by activating presynaptic 5-HT autoreceptors, thus decreasing the availability of Ca2+ for stimulus-release coupling.

Effect of Ergotamine on Serotonin-Mediated Responses in the Rodent and Human Brain

“…It has been previously demonstrated in vitro and in vivo that the activation of terminal 5-HT autoreceptors decreases the release of 5-HT (Chaput et al 1986, Göthert andWeinheimer 1979;Blier et al 1989). In the present study, ergotamine produced a concentrationdependent inhibition of the electrically evoked release of [ 3 H]5-HT from preloaded hypothalamus slices prepared from rats and guinea pigs.…”

Functional Pharmacology in Human Brain

“…The inhibition was prevented by methiothepin, a broad spectrum 5-HT receptor antagonist (Schlicker et al, 1985). These results show that release-inhibiting presynaptic 5-HT autoreceptors, previously found to be present in the rat brain (Cerrito and Raiteri, 1979;Göthert and Weinheimer, 1979), also exist in the human brain.…”

Role of serotonin transporter function in rat orbitofrontal cortex in impulsive choice

“…Further, 5-HT release is regulated, at least in part, by activation of pre- and post-synaptic 5-HT receptors [44]. Specifically, 5-HT 1A and 5-HT 1B autoreceptors, which are highly expressed in PFC, inhibit 5-HT neuronal firing and 5-HT release from terminals [44–47]. Also, postsynaptic receptor subtypes are located on non-5-HT neurons, which modulate 5-HT neuronal activity and release through neural inputs to 5-HT neurons [48].…”