Involvement of dopamine D(2) receptor in the diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in female rats

BACKGROUND: An endogenous dopaminergic (DA) tone acting on D(3) receptors has been shown to inhibit tuberoinfundibular (TI) DA neuron activity and stimulate prolactin (PRL) surge in the afternoon of estrogen-primed ovariectomized (OVX+E(2)) rats. Whether D(2) receptor (D(2)R) is also involved in the regulation of TIDA and PRL rhythms was determined in this study. RESULTS: Intracerebroventricular (icv) injection of PHNO, a D(2)R 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 D(2)R 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 D(2)R 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 D(2)R rhythm was abolished in OVX+E(2) 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 D(2)R mRNA for 2 days significantly reduced D(2)R 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 D(2)R mRNA expression was also observed in midbrain DA neurons and the rhythm was significantly knocked down by the AODN pretreatment. CONCLUSIONS: We conclude that a diurnal change of D(2)R mRNA expression in MBH may underlie the diurnal rhythms of TIDA neuron activity and PRL secretion in OVX+E(2) rats.