An endogenous dopaminergic tone acting on dopamine D3 receptors may be involved in diurnal changes of tuberoinfundibular dopaminergic neuron activity and prolactin secretion in estrogen-primed ovariectomized rats.

The diurnal rhythm of tuberoinfundibular dopaminergic (TIDA) neuron activity, i.e., high in the morning and low in the afternoon, is prerequisite for the afternoon prolactin (PRL) surge in proestrous and estrogen-primed ovariectomized (OVX) female rats. Whether dopamine acts via D(3) receptors in regulating the rhythmic TIDA neuron activity and PRL secretion in estrogen-primed OVX (OVX+E(2)) rats is the focus of this study. Intracerebroventricular (icv) injection of a D(3) receptor agonist, PD128907 (0.1-10 μg/3 μl), in the morning significantly reduced the basal activity of TIDA neurons and increased plasma PRL level. The effects of PD128907 were reversed by co-administration of U99194A, a D(3) receptor antagonist, but not by raclopride, a D(2) receptor antagonist. To determine whether endogenous dopamine acts on D(3) receptors involved in the diurnal changes of the activities, we used both U99194A, a D(3) receptor antagonist, and an antisense oligodeoxynucleotide (ODN) against D(3) receptor mRNA in the study. U99194A (0.1 μg/3 μl, icv) given at 1200 h significantly reversed the lowered TIDA neuron activity and the afternoon PRL surge at 1500 h. Moreover, OVX+E(2) rats pretreated with the antisense ODN (10 μg/3 μl, icv) for 2 days had the same effects as the D(3) receptor antagonist on TIDA neuron activity and the PRL surge. The same treatment with sense ODN had no effect. In conclusion, an endogenous DA tone may act on D(3) receptors to inhibit TIDA neuron activity and in turn stimulate the PRL surge in the afternoon of OVX+E(2) rats.