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

Abstract

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_2A 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-HT₂ 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-HT₁ 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_2A receptor, appears to exhibit an inhibitory effect on TIDA neuronal activity during the afternoon, which is essential for the PRL surge.

Activation of 5-HT2A receptor disrupts rat maternal behavior

“…In addition, the 5-HT 2A receptor system and various sex hormones (e.g. estrogen, prolactin) that are fundamentally important for maternal behavior show various reciprocal interactions (Fink et al, 1996; Liang and Pan, 2000). Thus, it is logic to think that this receptor system should play a role in maternal behavior.…”

Effects of serotonin injected into the third ventricle on prolactin and growth hormone secretion in Holstein steers

“…According to these results, it is highly likely that 5‐HT injected into 3V induces the stimulation of PRL release as a consequence of the suppression of DA neuron activity. It has been also reported that 5‐HT 2A antagonist blocked falls in tuberoinfundibular DA neuronal activity followed by afternoon PRL surge, that 5‐HT 2A agonist induced DA activity and the increase in PRL, and that 5‐HT 1 agonist did not alter DA neuronal activity and PRL release (Liang & Pan 2000). Therefore the inhibition of DA followed by the increase in PRL release appears to occurred via 5‐HT 2A receptors.…”

“…Since the microinjection of 5-HT into the medial basal hypothalamus signifi-cantly increased PRL release (Willoughby et al 1988), it is reasonable to consider that tuberoinfundibular DA neurons play an important role in the stimulation of PRL release by 5-HT. Liang and Pan (2000) clarified the relationship between 5-HT receptors and tuberoinfundibular DA neurons which is important for estrogen-induced PRL surge in rats. According to these results, it is highly likely that 5-HT injected into 3V induces the stimulation of PRL release as a consequence of the suppression of DA neuron activity.…”

Involvement of dopamine D2 receptor in the diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in female rats

“…Dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ME, dlST and NA were determined by HPLC with electrochemical detection as previously described [3,8,9,19]. Protein contents in punched brain tissues used for HPLC were measured by the Lowry method [20].…”