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The Journal of Neuroscience, December 1, 1998, 18(23):10189-10195

Mating-Related Stimulation Induces Phosphorylation of Dopamine- and Cyclic AMP-Regulated Phosphoprotein-32 in Progestin Receptor-Containing Areas in the Female Rat Brain

John M. Meredith¹, Christopher A. Moffatt², Anthony P. Auger², Gretchen L. Snyder³, Paul Greengard³, and Jeffrey D. Blaustein²

¹ Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, Arkansas 72079, ² Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, and ³ Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021

Vaginal-cervical stimulation induces a number of physiological and behavioral events, including the facilitation of mating behavior. Although the facilitation of one component of mating behavior, lordosis, by vaginal-cervical stimulation does not require the presence of progesterone, it appears to be mediated by neural progestin receptors. Abundant evidence suggests that dopamine may play a role in the neural circuitry activated by vaginal-cervical stimulation, including the mating-induced release of dopamine in progestin receptor-containing areas of the brain, changes in the activational state of progestin receptors because of dopamine D₁ receptor stimulation, facilitation of lordosis by D₁ receptor stimulation in estradiol-primed rats via progesterone-independent events, and D₁ agonist-induced neuronal responses in progestin receptor-containing areas and cells. We tested the hypothesis that vaginal-cervical stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32; M_r = 32,000), a protein phosphorylated predominantly in response to the stimulation of D₁ receptors. At 9 d after ovariectomy, female rats were injected subcutaneously with a behaviorally effective dose of estradiol benzoate. At 48 hr later they received vaginal-cervical or control (perineal) stimulation, and they were perfused 1 hr later. Vaginal-cervical stimulation increased the number of cells expressing pDARPP-32 immunoreactivity by 92% in the medial preoptic nucleus, 134% in the caudal ventromedial hypothalamic nucleus, 123% in the posterodorsal medial amygdala, and 103% in the bed nucleus of the stria terminalis. These results suggest that some of the neuronal effects of vaginal-cervical stimulation, and perhaps other social or environmental stimuli, are mediated by phosphorylation of DARPP-32, perhaps via stimulation of D₁ receptors, within progestin receptor-containing areas.

Key words: vaginal-cervical stimulation; cervical stimulation; dopamine; estradiol; progestin receptors; phosphorylation; DARPP-32

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Copyright © 1998 Society for Neuroscience  0270-6474/98/182310189-07$05.00/0

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