Pharmacological Evidence that Serotonergic Stimulation of Prolactin Secretion is Mediated via the Dorsal Raphe Nucleus

Abstract

Administration of the serotonin-releasing drug DL-p-chloroamphetamine (PCA) to rats caused a dose-dependent increase in plasma prolactin levels. The effect was maximal 2 h after administration. The effect of PCA was prevented by prior administration of the serotonin synthesis inhibitor p-chlorophenylalanine-methyl ester (PCPA). PCPA pre-treatment did not prevent the increase in plasma prolactin levels after administration of the serotonin agonist quipazine which is consistent with a postsynaptic receptor interaction of quipazine. To determine which serotonergic neurons are involved, the prolactin responses to PCA were determined in rats sustaining lesions of the dorsal or median raphe nuclei. The lesions were produced in desmethylimipramine-pretreated rats by local injections of 5,7-dihydroxytryptamine (5,7-DHT) 2 weeks prior to the PCA challenge. In rats with dorsal raphe lesions, the effect of PCA on prolactin secretion was significantly attenuated. In contrast, median raphe lesions did not prevent the effect of PCA on plasma prolactin levels. In summary, these data support the hypothesis that release of serotonin increases prolactin secretion. In addition, these data suggest that serotonergic neurons in the dorsal raphe nucleus are part of a neural pathway which can mediate increases in prolactin secretion.

Regulation of Progestin Receptors in Raphe Neurons of Steroid-Treated Monkeys

“…The average serum prolactin levels (ng/ml) after P implantation (days [15][16][17][18][19][20][21][22][23][24][25][26][27][28] in all of the monkeys whose pontine tissue blocks were used in this study equaled 35.6 ± 1.6 in the spayed group, 31.7 ± 3.6 in the E-treated group, and 120.4 ± 13.5 in the E+P-treated group. Only the E+P treatment caused a significant increase in serum prolactin (p < 0.001).…”

“…In addition, serotonin antag onists for 5HT-lb receptors block prolactin secretion pro moted by administration of a serotonin releaser, fenflur amine [ 14], or by 5HT agonists [15]. Finally, lesion of the dorsal raphe in rats abolishes prolactin release induced by pretreatment with the serotonin releaser, PCA [16], and produces supersensitivity in the prolactin dose response to the 5HT agonist, RU24969 [17].…”

Effects of Clonidine on Blood Pressure, Noradrenaline, Cortisol, Growth Hormone, and Prolactin Plasma Levels in High and Low Intestinal Tone Depressed Patients

“…In this respect, the fact that both CRT and PRL mean plasma levels were greater in high-IT depressed patients than in low-IT depressed patients, during pre-clonidine pe riods, suggests the stimulating role that the serotonergic system might play in releasing these hypothalamic factors in the former group. In effect, it is a well-known fact that the central serotonergic system is involved in the releasing of corticotrophin-releasing hormone and triggers PRLreleasing mechanisms [3,9,20,22,24,25,31]. Furthermore, the proven fact that fenfluramine (a serotonin depletor agent) [10] is able to induce a quick improvement of high-IT depressed patients [18] provides additional reinforcement to this presumption.…”

Effects of Serotonin Depletion by p-Chlorophenylalanine, p-Chloroamphetamine or 5,7-Dihydroxytryptamine on Central Dopaminergic Neurons: Focus on Tuberoinfundibular Dopaminergic Neurons and Serum Prolactin

“…The fact that the release of both 5-HT and DA can be stimulated by PCA may explain the delayed response of PRL (at 60 min only) and the inconsistency between ME DOPAC/5-HIAA and serum PRL levels. An earlier study suggested that PCAinduced PRL release appears to be mediated by increased 5-HT release since prior depletion of central 5-HT prevents PCA's effect [37]. Nevertheless, the PCA-induced PRL secretion should be the net effect of 5-HT, 5-HTstimulated PRF, and DA.…”