Summary
The overflow of tritium from stimulated rat hypothalamic slices preincubated with [3H]-serotonin (5-HT) was significantly enhanced by reducing the frequency of stimulation from 3 Hz to 1 Hz while keeping the number of impulses constant. The 5-HT receptor agonist 5-methoxytryptamine inhibited in a concentration-dependent manner the electrically-evoked release of [3H]-5-HT with IC50 values of 560 nmol/l and of 34 nmol/l when the stimulations were delivered at 3 Hz and 1 Hz, respectively. The terminal 5-HT autoreceptor antagonist methiothepin enhanced in a concentration-dependent manner the electrically-evoked release of [3H]-5-HT and this effect was greater at a frequency of stimulation of 3 Hz than at 1 Hz. In the same paradigm, the 5-HT reuptake inhibitors citalopram and paroxetine did not alter the overflow of radioactivity elicited by stimulation at 3 Hz but significantly decreased it at 1 Hz. In the presence of 5-HT autoreceptor blockade achieved with methiothepin, citalopram increased the overflow of [3H]-5-HT to the same extent at 1 Hz and at 3 Hz. The IC50 values for inhibition of [3H]-5-HT release by the selective α2-adrenoceptor agonist UK 14.304 were 35 nmol/l at 3 Hz and 30 nmol/l at 1 Hz. It is concluded that modulation of 5-HT release by 5-HT autoreceptors, but not by α2-adrenoceptors is dependent on the synaptic concentration of 5-HT as a function of the frequency of depolarization.
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References
Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central-nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43
Blier P, Chaput Y, de Montigny C (1988) Long-term 5-HT reuptake blockade, but not monoamine oxidase inhibition, decreases the function of terminal 5-HT autoreceptor: an electrophysiological study in the rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 337:246–254
Blier P, Galzin AM, Langer SZ (1989) Diurnal variation in the function of serotonin terminals in the rat hypothalamus. J Neurochem (in press)
Cambridge D (1981) UK-14,304 — a potent and selective α2-agonist for the characterization of α-adrenoceptor subtypes. Eur J Pharmacol 72:413–415
Cerrito F, Raiteri M (1979) Serotonin release is modulated by presynaptic autoreceptors. Fur J Pharmacol 57:427–430
Chaput Y, Blier P, de Montigny C (1986) In vivo electrophysiological evidence for the regulatory role of autoreceptors on serotoninergic terminals. J Neurosci 6:2796–2801
Chaput Y, de Montigny C (1988) Effects of the 5-hydroxytryptamine1 receptor antagonist, BMY 7378, on 5-hydroxytryptamine neurotransmission: electrophysiological studies in the rat central nervous system. J Pharmacol Exp Ther 246:359–370
De Lean A, Munsen PJ, Rodbard D (1978) Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay and physiological dose-response curve. Am J Physiol 235:97–102
Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K (1986) Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch Pharmacol 332:1–7
Farnebo LO, Hamberger B (1974) Regulation of 3H-5-hydroxy-tryptamine release from rat brain cortex slices. J Pharm Pharmacol 26:642–644
Feuerstein TJ, Lupp A, Hertting G (1987) The serotonin (5-HT) autoreceptor in the hippocampus of the rabbit: role of 5-HT biophase concentration. Neuropharmacology 26:1071–1080
Galzin AM, Langer SZ (1986) Potentiation by deprenyl of the autoreceptor-mediated inhibition of [3H]-5-hydroxytryptamine release by 5-methoxytryptamine. Naunyn-Schmiedeberg's Arch Pharmacol 333:330–333
Galzin AM, Moret C, Langer SZ (1984) Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha-2 adrenoceptor on serotonergic nerve endings in the rat hypothalamus. J Pharmacol Exp Ther 228:725–732
Galzin AM, Moret C, Verzier B, Langer SZ (1985) Interaction between tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitors and the presynaptic 5-hydroxytryptamine inhibitory autoreceptors-in the rat hypothalamus. J Pharmacol Exp Ther 235:200–211
Göthert M (1980) Serotonin receptor-mediated modulation of Ca2+ dependent 5-hydroxytryptamine release from rat brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 314:223–230
Jacobs BL (1985) An overview of brain serotonergic unit activity and its relevance to the neuropharmacology of serotonin. In: Green AR (ed) The neuropharmacology of serotonin. Oxford University Press, Oxford, pp 196–217
Langer SZ, Moret C (1982) Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. J Pharmacol Exp Ther 222:220–226
Maura G, Roccatagliata E, Raiteri M (1986) Serotonin autoreceptors in rat hippocampus: pharmacological characterization as a subtype of the 5-HT1 receptor. Naunyn-Schmiedeberg's Arch Pharmacol 334:323–326
Richards MH (1985) Efflux of 3H-5-hydroxytryptamine from rat hypothalamic slices by continuous electrical stimulation: frequency-dependent responses to serotonergic antagonists and 5-hydroxytryptamine. Naunyn-Schmiedeberg's Arch Pharmacol 329:359–366
Sills MA, Wolfe BB, Frazer A (1984) Determination of selective and non selective compounds for the 5-HT1A and 5-HT1B receptor subtypes in rat frontal cortex. J Pharmacol Exp Ther 231:480–487
Thomas DR, Nelson DR, Johnson AM (1987) Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 93:193–200
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Blier, P., Ramdine, R., Galzin, AM. et al. Frequency-dependence of serotonin autoreceptor but not α2-adrenoceptor inhibition of [3H]-serotonin release in rat hypothalamic slices. Naunyn-Schmiedeberg's Arch Pharmacol 339, 60–64 (1989). https://doi.org/10.1007/BF00165127
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DOI: https://doi.org/10.1007/BF00165127