Partial Characterization of a Neurotransmitter Pathway Regulating the in vivo Release of Prolactin

Abstract

Nicotinic cholinergic, opiate and serotonergic agonists as well as dopaminer-gic antagonists induce the release of pituitary prolactin. The purposes of the present studies were to determine if nicotine, morphine and the serotonin _1A (5-HT_1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) utilize a common synaptic pathway to release prolactin and, if so, to establish the serial order of the receptors involved. We also sought to determine whether the pathway under investigation leads to the secretion of prolactin via a mechanism involving dopamine, the prolactin inhibitory factor. Male rats with indwelling jugular catheters were pretreated with saline, mecamylamine, naltrexone, methysergide or bromocriptine. In the saline-treated animals, administration of nicotine, morphine, 8-OH-DPATand haloperidol resulted in significant increases in plasma prolactin levels. Mecamylamine pretreatment prevented the prolactin response to nicotine only. N-altrexone blocked the stimulation of prolactin release by morphine and by nicotine. Methysergide inhibited the effects of 8-OH-DPAT, morphine and nicotine but not haloperidol. Bromocriptine blocked the prolactin secretion induced by haloperidol as well as by each of the above agonists. Also, in dual-immunocytochemically stained sections, tyrosine hydroxylase-immunoreactive cells and serotonin-immunoreactive processes were detected in close anatomical proximity in the dorsomedial arcuate nucleus. These data indicate that nicotine, morphine and 8-OH-DPAT act to release prolactin via a common synaptic pathway expressing nicotinic cholinergic, opiate, and 5-HT_1A receptors at synapses arranged serially in that functional order. Furthermore, the data indicate that the in vivo secretion of prolactin via this pathway may ultimately occur through the inhibition of dopamine release.

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

“…The demonstration of enhanced PRL secretion ln response to fleslnoxan ls consistent wlth earller reports that 8-0H-DPAT ellclts PRL release ln rats (Stmonovlc et al 1984;Willoughby et al 1988;Aulakh et al 1988;Dl Sclullo et al 1990;Kellar et al 1992;Flores et al 1992), whlch ls blocked by methyserglde or metergoline (Willoughby et al 1988;Aulakh et al 1988;Kellar et al 1992). In hllmans, lncreased PRL secr~tion was reported wlth busplrone (Meltzer et al 1983;Coccaro et al 1990;Anderson and Cowen, 1992), geplrone ), but no: wlth lpsaplrone (Lesch et al 1989) or tandosplrone (Miller et al 1990).…”

“…The 8-0H-DPAT administration induced PRL release (Slmonovic et al 1984;Willoughby et al 1988;Aulakh et al 1988;Di Sciullo et al 1990;Kellar et al 1992;Flores et al 1992). The effect of 8-0H-DPAT most likely involves 5-HT pathways since pretreatment with • methysergide or metergoline blocked the 8-0H-DPAT-induced PRL release (Willoughby et al 1988;Kellar et al 1992;Jorgensen et al 1993;Flores et al 1992) while these antagonists failed to attenuaie the PRL secretion induced by the DA antagonist haloperidol Ellis et al 1991). In addition.…”

Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects

“…At the time of the increase in dopamine, an increase in plasma fenfluramine and norfenfluramine levels and prolactin concentrations was observed. It has been hypothesized that the ability of fenfluramine to release prolactin is indicative of an interaction between serotonin and dopamine (31). However, serotonin may also stimulate prolactin release directly (32).…”

Neurotransmitters Involved in the Opioid Regulation of Prolactin Secretion at the End of Pregnancy in Rats

“…Although the stimulatory effect of serotonin on prolactin secretion is well documented [28], there are evidences that, under certain physiological or experimental conditions, activation of the serotoninergic system can also inhibit prolactin secretion, particularly at the end of pregnancy [4, 30, 31, 32, 33]. Previous studies reported that opioids increase the 5-HT turnover in the hypothalamus [68]and that stimulation of prolactin release depends upon intact serotoninergic neurotransmission [69, 70]. Moreover, immunocytochemical studies have shown that serotoninergic endings make synaptic contacts with POMC neurons in the arcuate nucleus [71].…”