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      An Endogenous Serotonergic Rhythm Acting on 5-HT 2A Receptors May Be Involved in the Diurnal Changes in Tuberoinfundibular Dopaminergic Neuronal Activity and Prolactin Secretion in Female Rats

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          The central serotonergic system has long been known to have a stimulatory role on the secretion of prolactin (PRL). The integrity of serotonergic neurotransmission is essential for the expression of the estrogen-induced afternoon PRL surge. Whether its effect on PRL involves change in the activity of tuberoinfundibular dopaminergic (TIDA) neurons has not been ascertained. In adult ovariectomized rats treated with estrogen, depletion of central serotonin (5-HT) by 5,7-dihydroxytryptamine (5,7-DHT, 200 µg/rat, i.c.v.) effectively prevented the afternoon fall in TIDA neuronal activity (using the levels of 3,4-dihydroxyphenylalanine and 3,4-dihydroxyphenylacetic acid (DOPAC), and the ratio of DOPAC/dopamine in the median eminence as indices), and blunted the afternoon PRL surge. A single injection of a 5-HT<sub>2A</sub> receptor antagonist, ketanserin (5 mg/kg, i.p. at 12.00 h), also had the same effects on the diurnal changes in TIDA neuronal activity and PRL secretion as the treatment with 5,7-DHT did. Intracerebroventricular injection of a 5-HT<sub>2</sub> receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) in the morning inhibited the TIDA neuronal activity and stimulated PRL secretion in a dose-dependent manner; while injection of a 5-HT<sub>1</sub> agonist, 8-hydroxy-dipropylaminotetralin, was without effect. Injection of DOI in 5,7-DHT-pretreated rats at 14.30 h also lowered the TIDA neuronal activity and reinstated the PRL surge. In all, endogenous 5-HT, acting through the 5-HT<sub>2A</sub> receptor, appears to exhibit an inhibitory effect on TIDA neuronal activity during the afternoon, which is essential for the PRL surge.

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          Most cited references 13

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          Central dopaminergic neurons: Effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid

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            Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis.

            The effects of local application of serotonin (5-HT) on extracellular levels of dopamine (DA) in the nucleus accumbens (N. ACC) were assessed using in vivo microdialysis. At a perfusate flow rate of 0.3 microliter/min the baseline dialysate concentration of DA was 2.1 +/- 0.7 nM (mean +/- S.E.M.; n = 5) and significantly increased to 142 +/- 18%, 220 +/- 47% and 332 +/- 35% of baseline when 0.1 microM, 0.2 microM and 0.4 microM concentrations of 5-HT were included in the perfusate. Perfusate 5-HT concentrations below 0.1 microM had no effect on dialysate DA. The in vivo dialysis efficiency for 5-HT was found to be 39 +/- 12%, and thus the concentrations of 5-HT reaching the extracellular space at the surface of the dialysis membrane were estimated to be 40, 80 and 160 nM for the 0.1, 0.2 and 0.4 microM 5-HT perfusates, respectively. The serotonin-induced increase in dialysate DA was attenuated by co-perfusion of 0.4 microM 5-HT with 4 microM concentrations of pindolol (a relatively non-specific 5-HT1 antagonist; 151 +/- 7% vs. 332 +/- 35% baseline dialysate DA for 5-HT/antagonist and 5-HT-only perfusates, respectively), LY 53,857 (a specific 5-HT2 antagonist; 130 +/- 17% vs. 332 +/- 35%) and MDL 7222 (a specific 5-HT3 antagonist; 143 +/- 19% vs. 332 +/- 35%).(ABSTRACT TRUNCATED AT 250 WORDS)
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              The metabolism of dopamine in the median eminence reflects the activity of tuberoinfundibular neurons.

              The purpose of the present study was to characterize the metabolism of dopamine (DA) in tuberoinfundibular (TI) neurons terminating in the median eminence and to examine the effects of procedures that alter the synthesis and turnover of DA in these neurons on the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence. The DA uptake inhibitor nomifensine (25 mg/kg, i.p.; 30 min) failed to alter median eminence DOPAC concentrations indicating that very little released DA is recaptured and metabolized by TIDA neurons. Within 5 min following the administration of the monoamine oxidase inhibitor pargyline (50 mg/kg, i.v.) median eminence DOPAC concentrations declined to 15% of control demonstrating that this metabolite has a high turnover rate and is rapidly removed from the median eminence. Median eminence DOPAC concentrations in diestrous female rats, whose TIDA neuronal activity is higher than in the male, were two-fold greater than in male rats. Prolactin (10 micrograms/rat, i.c.v.; 12 h), which increases TIDA neuronal activity, produced a corresponding increase in median eminence DOPAC concentrations in male rats. Restraint stress (30 min), which decreases TIDA neuronal activity, produced a corresponding decrease in median eminence DOPAC concentrations in diestrous female rats. The results from the present study suggest that DOPAC concentrations in the median eminence can be used as an index of TIDA neuronal activity.

                Author and article information

                S. Karger AG
                July 2000
                23 July 2000
                : 72
                : 1
                : 11-19
                Department of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC
                54566 Neuroendocrinology 2000;72:11–19
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 7, References: 36, Pages: 9
                Prolactin and Reproductive Hormones


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