Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: Anatomical support for its involvement in the central effects of vasopressin

Biological effects of vasopressin (VP) are mediated by four different receptors, two of which (the Via and the oxytocin receptors) have been well characterized in the rodent brain, suggesting that these are the main receptors responsible for the central effects of VP. However, transcripts of the V1b VP receptor (V1bR) have been detected throughout the rat brain by RT-PCR and in situ hybridization, indicating that the V1bR adds to the population of central VP receptors. Because there are no specific ligands for the V1bR, the receptor protein itself has been difficult to visualize. In the present study, the distribution of the V1bR protein was investigated in the rat forebrain, midbrain, hindbrain, and cerebellum by immunohistochemistry using an antiserum raised against a synthetic fragment of the carboxylterminal of the rat V1bR protein. Immunohistochemistry revealed the presence of the V1bR in pituitary corticotrophs as expected. In naive, untreated rats, fiber networks containing V1bR-immunoreactivity were mainly concentrated in the hypothalamus, amygdala, cerebellum, and particularly in those areas with a leaky blood brain barrier or close to the circumventricular organs (medial habenula, subfornical organ, organum vasculosum laminae terminalis, median eminence, and nuclei lining to the third and fourth ventricles). A strikingly dense network was present in the external zone of the median eminence. Colchicine treatment was required to reveal the localization of V1bR-immunoreactive cell bodies. V1bR-containing cell bodies and associated protrusions were mainly located in the hippocampus, caudate putamen, cortex, thalamus, olfactory bulb, and cerebellum. These results demonstrate the widespread distribution of the V1bR protein in the rat brain over multiple, functionally distinct neuronal systems. These data suggest that the V1bR mediates different physiological functions of VP in the brain.