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

Abstract

Using a pharmacological approach, we explored potential mechanisms for the regulation of prolactin secretion by opioid peptides at the end of pregnancy in rats. On day 19 of pregnancy, intracereboventricular administration of the µ-opioid receptor agonist (D-Ala², NMe-Phe⁴, Gly-ol⁵)-enkephalin (DAMGO) or β-endorphin (β-END) induced a dose-related increase in serum prolactin levels 30 min later. Pretreatment with the opioid antagonist naloxone abolished the increase induced by DAMGO injection. At lower doses, DAMGO and β-END did not modify the 3,4-dihydroxyphenylacetic acid/dopamine ratio, but at higher doses, the µ-agonists evoked a significant increase of the dopaminergic activity as compared with saline control. The time course of the effects of β-END (2.5 µg/rat) showed a higher increase in serum prolactin levels at 15 min than at 30 min after treatment. The 3,4-dihydroxyphenylacetic acid/dopamine ratio increased 15 min after β-END administration and was even higher 30 min later. Neither the selective ĸ-agonist U50,488H nor the selective δ-agonist (D-Pen², D-Pen⁵)- enkephalin were able to modify the serum prolactin levels at the doses studied.To evaluate potential neurotransmitters involved in the regulation of prolactin secretion at the end of pregnancy, we combined the administration of serotoninergic or GABAergic antagonists with the opioid agonist DAMGO. The serotonin 5-HT₂ receptor antagonist ketanserin increased the serum prolactin levels and potentiated the effect of DAMGO. The intracerebroventricular administration of SR-95531 did not modify the serum prolactin concentration under basal conditions, but partially prevented the increase induced by DAMGO injection. The intracerebroventricular administration of the GABA_B receptor antagonist phaclofen had no effect on the serum prolactin levels either in naive or DAMGO-treated rats. The present results support the proposal that activation of µ-opioid receptors stimulates prolactin secretion at the end of pregnancy. Although the exact mechanisms by which the opioid system modulates prolactin secretion at the end of pregnancy are unclear, these results suggest an interaction of the opioidergic system with serotoninergic and GABAergic systems, without ruling out a direct or indirect action on dopaminergic neurons. In conclusion, the opioid system may regulate prolactin secretion at the end of pregnancy through either stimulatory (present results) or inhibitory actions previously described.

Dopaminergic Mechanisms Involved in Prolactin Release after Mifepristone and Naloxone Treatment during Late Pregnancy in the Rat

“…In short, at late pregnancy two opioid influences may regulate prolactin secretion, a stimulatory action that acts through a direct or indirect inhibition of dopaminergic transmission [6, 11] and an inhibitory action that becomes observable after the reduction in progesterone action has diminished dopaminergic transmission. This inhibitory action would be exerted on non-dopaminergic neuronal systems participating in prolactin regulation.…”

“…In pregnant rats, the opioid system modulates prolactin secretion in a complex manner. Both stimulatory and inhibitory actions of opioids may result, acting through different regulatory pathways, in an elevation of prolactin levels [6,7,8,9,10,11]. Interestingly, progesterone plays an important role in this regulation.…”

Dorsal hippocampal N‐methyl‐d‐aspartate glutamatergic and δ‐opioidergic systems modulate anxiety behaviors in rats in a noninteractive manner

“…5 mg/rat, and 0.75 mg/rat) [22,23] and four other groups received NMDA receptor antagonist MK801 (0.25 mg/rat, 0.5 mg/rat, 0.75 mg/rat, and 1 mg/rat) [22] and were compared with saline control group. Experiment 2: effects of d-opioid receptor agonist and antagonist on anxiety-like behavior Four groups of rats received bilateral dorsal hippocampus injection (intra-CA1) of selective d receptor agonist enkephalin (1 mg/rat, 2 mg/rat, 5 mg/rat, and 10 mg/rat) [24,25], and four other groups received d receptor antagonist naltrindole hydrochloride (0.25 mg/rat, 0.5 mg/rat, 1 mg/rat, and 2 mg/ratdintra-CA1) [26,27]. These rats were thereafter compared with a saline control group.…”

Treatment with steroid hormones and morphine alters general activity, sexual behavior, and opioid gene expression in female rats

“…The regulation of the secretion of pituitary gonadotropins results from a complex interplay between the feedback effects of gonadal steroids and influence exerted by brain neurotransmitters in the hypothalamic-pituitary-adrenal axis (Motta et al, 1969;Kalra, 1993;Xu et al, 1993;Soaje et al, 2004;Maccari and Morley-Fletcher, 2007). Studies have shown that this phenomenon involves brain opioids that exert an inhibitory influence on gonadotropin secretion (Kalra, 1993;Funabashi et al, 2010;Tavakoli-Nezhad and Arbogast, 2010).…”