Mating-induced changes in signal transduction in limbic regions of female rats

The molecular mechanisms that initiate pseudopregnancy (PSP) are largely unknown, but the neuroendocrine processes required for PSP share certain similarities to long-term memory (LTM) formation. LTM involves the phosphorylation of MAPK (pMAPK) and its translocation to the nucleus where it phosphorylates CREB (pCREB), which then interacts with the transcriptional machinery. The aim of these experiments was to determine if mating-related vaginocervical stimulation (VCS), which is necessary to induce PSP, activates the mitogen-activated protein kinase (MAPK) and cAMP response element binding protein (CREB) pathway in hypothalamic and limbic regions known to be important for PSP in female rats (Rattus norvegicus).;Ninety minutes after mating, pCREB intensity and/or the number of pCREB-immunoreactive neurons increased in the hippocampal CA1, CA3, and dentate gyrus regions, the posterodorsal medial (MEPD) and basolateral amygdala regions, and the ventrolateral division of the ventromedial hypothalamus. At least part of the increase in pCREB neurons in the MEPD after mating can be attributed to olfactory/pheromonal cues because exposure to male-soiled bedding alone increased pCREB selectively in this region. These data suggest that VCS, together with olfaction and somatosensation (flank and perineal stimulation), may contribute to elevated pCREB expression in the MEPD, whereas the mating-induced increase in pCREB neurons in other brain regions requires physical contact with the male.;In contrast to pCREB, mating-induced changes in the phosphorylation and subcellular localization of pMAPK were observed only in the dentate gyrus. Co-labeling of cytoplasmic pMAPK and CREB in the dentate gyrus increased 90 minutes after mating, but the lack of effect in other regions, particularly the MEPD, indicates that changes in pCREB are not invariably dependent upon phosphorylation by pMAPK. The observed patterns of pCREB expression after mating are consistent with its proposed role in animal models of anxiety and depression, but not with learning models as originally hypothesized. These data further suggest that pCREB signaling may be involved in processing the rewarding aspects of mating not associated with VCS per se. These findings may contribute to understanding the role of pCREB in abnormal sexual behavior associated with anxiety and depression.