Neuroanatomical specificity of prolactin-induced hyperphagia and expression of fos-like immunoreactivity following central administration of prolactin

The present experiments extend our understanding of the orexigenic properties of prolactin (PRL) in female rats. PRL is known to increase food intake in virgin female rats when injected intracerebroventricularly (icv) but it is not known where in the brain PRL acts to promote feeding behavior. The first series of studies investigated the role of the paraventricular nucleus (PVN), ventromedial nucleus (VMH), and medial preoptic nucleus (MPOA) in the hyperphagic actions of PRL. Ad libitum fed virgin female rats received twice daily site-specific injections of PRL (800 ng) over a period of 10 days. Only subjects demonstrating regular vaginal cyclicity were included in the study. Food intake, body weight, and vaginal cyclicity were measured daily. Results showed that PRL significantly increased food intake when injected in the PVN. A nonsignificant trend towards a hyperphagic response in the last 5 days of testing was observed in rats receiving intra-VMH injections of PRL, and the MPOA was not responsive to the feeding stimulating properties of PRL. None of the manipulations affected body weight or vaginal cyclicity as demonstrated by vaginal smears. In sum, although it is possible that PRL action may occur at other sites, the present results reveal that PRL acts through the PVN to induce feeding in virgin female rats. A second experiment investigated the pattern of cellular activation, as revealed by Fos-like immunoreactivity (Fos-lir), in the PVN, VMH, and MPOA of female rats following treatments of varying lengths of icv administration of PRL. Ad libitum fed virgin female rats were given 1, 7 or 15 icv injections of PRL twice daily at a dose known to promote hyperphagia (2 [Special characters omitted.] /0.5 [Special characters omitted.] ). The rats were sacrificed one hour after their last injection and their brains processed for Fos-fir. Significant changes in expression of Fos-lir were observed only in the PVN of rats having received 15 injections of PRL. Therefore the PVN is the hypothalamic site most responsive to the effect of PRL on feeding behavior, and the one in which most cellular activation was observed after chronic administration of PRL. Given that PRL can upregulate its own receptors, and that PRL effects in the brain occur by PRL binding to its receptors, it is plausible to suggest that significant increases in the expression of Fos-lir in the PVN of rats after prolonged icv administration of PRL may reflect an upregulation of PRL receptors. Suggestions for future studies that would elaborate on these results are proposed. These are the first tests of the site-specificity of the central effect of PRL on feeding in rats, and of the expression of Fos-lir in selected hypothalamic sites after a varying number of icv injections of PRL. It is concluded that PRL plays a significant role in the PVN to promote feeding and cellular activation as evidenced by both behavioral and immunohistochemical dat