Neurochemical properties of the prolactin releasing peptide (PrRP) receptor expressing neurons: Evidence for a role of PrRP as a regulator of stress and nociception

In addition to its stimulatory effect on prolactin release, the neuropeptide prolactin releasing peptide (PrRP) has been shown to be a mediator of the stress response. To analyze the neurochemical properties of the cells responsive to PrRP and involved in stress modulation, we examined PrRP receptor co-expression with two neuropeptides involved in stress, corticotropin releasing hormone (CRH) and enkephalin (ENK). We find that although PrRP receptor is highly expressed in the parvocellular division of the paraventricular nucleus of hypothalamus (PVN), the majority of the cells expressing PrRP receptor are neither CRH- nor ENK-positive. The only region where the PrRP receptor co-expresses extensively with CRH is the bed nucleus of the stria terminalis (BST). There is also a small number of cells positive for CRH and PrRP receptor in the central nucleus of amygdala (CEA), while the remaining PrRP receptor-positive cells co-express ENK. Furthermore we find that the PrRP receptor-expressing neurons in the brainstem parabrachial nucleus (PB) largely express ENK rather than CRH. From these results we propose a model in which PrRP modulates the hypothalamic-pituitary-adrenal axis through trans-synaptic modulation of hypothalamic CRH release rather than through direct activation of PVN neurons. We also suggest that PrRP may modulate nociception by virtue of its receptor's co-expression with ENK in PB. Our results provide a theoretical framework by which future studies examining the role of PrRP in brain could be elucidated.