Abstract

BackgroundAn endogenous dopaminergic (DA) tone acting on D3 receptors has been shown to inhibit tuberoinfundibular (TI) DA neuron activity and stimulate prolactin (PRL) surge in the afternoon of estrogen-primed ovariectomized (OVX+E2) rats. Whether D2 receptor (D2R) is also involved in the regulation of TIDA and PRL rhythms was determined in this study.ResultsIntracerebroventricular (icv) injection of PHNO, a D2R agonist, in the morning inhibited TIDA and midbrain DA neurons’ activities, and stimulated PRL secretion. The effects of PHNO were significantly reversed by co-administration of raclopride, a D2R antagonist. A single injection of raclopride at 1200 h significantly reversed the lowered TIDA neuron activity and the increased serum PRL level at 1500 h. Dopamine D2R mRNA expression in medial basal hypothalamus (MBH) exhibited a diurnal rhythm, i.e., low in the morning and high in the afternoon, which was opposite to that of TIDA neuron activity. The D2R rhythm was abolished in OVX+E2 rats kept under constant lighting but not in OVX rats with regular lighting exposures. Pretreatment with an antisense oligodeoxynucleotides (AODN, 10 μg/3 μl/day, icv) against D2R mRNA for 2 days significantly reduced D2R mRNAs in central DA neurons, and reversed both lowered TIDA neuron activity and increased serum PRL level in the afternoon on day 3. A diurnal rhythm of D2R mRNA expression was also observed in midbrain DA neurons and the rhythm was significantly knocked down by the AODN pretreatment.ConclusionsWe conclude that a diurnal change of D2R mRNA expression in MBH may underlie the diurnal rhythms of TIDA neuron activity and PRL secretion in OVX+E2 rats.

Highlights

  • An endogenous dopaminergic (DA) tone acting on D3 receptors has been shown to inhibit tuberoinfundibular (TI) DA neuron activity and stimulate prolactin (PRL) surge in the afternoon of estrogen-primed ovariectomized (OVX+E2) rats

  • We recently reported that DA acting on D3R inhibits basal tuberoinfundibular dopaminergic (TIDA) neuron activity, and an endogenous DA tone acting on D3R may be involved in the diurnal changes of TIDA neuron activities and PRL secretion in OVX+E2 rats [10]

  • Involvement of D2 receptor (D2R) in diurnal changes of TIDA neuron activity and PRL secretion in OVX+E2 rats The diurnal changes of TIDA neuron activity and serum PRL level were observed in artificial cerebrospinal fluid (aCSF)-injected rats in which median eminence (ME) dihydroxyphenylacetic acid (DOPAC)/DA ratio in the afternoon was significantly lower than that in the morning (p < 0.05; Figure 5) and serum PRL level in the afternoon was significantly higher than that in the morning (p < 0.01; Figure 5)

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Summary

Introduction

An endogenous dopaminergic (DA) tone acting on D3 receptors has been shown to inhibit tuberoinfundibular (TI) DA neuron activity and stimulate prolactin (PRL) surge in the afternoon of estrogen-primed ovariectomized (OVX+E2) rats. Intracerebroventricular (icv) injection of DA inhibits basal TIDA neuron activity in estrogen-primed ovariectomized (OVX+E2) rats [3]. The percentage of DA-inhibited dmARN neurons is significantly reduced (to 39-44%) in brain slices obtained from OVX+E2 rats pretreated with antisense oligodeoxynucleotides (AODN) against D2R or D3R mRNA for 2 days [6]. Combined treatment of both AODNs reduces the percentage even further (to 18%)

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