Vasopressin: behavioral roles of an "original" neuropeptide

Abstract

Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950s, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies have implicated Avp in the regulation of various social behaviors across species. Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made in understanding the role of Avp in regulating these and other behaviors across species. We also discuss the implications for human behavior.

Figure 1

Schematic diagram of the oxytocin and vasopressin genes (top, large arrows) preprohormones (middle boxes) and peptides (bottom). Both genes are composed of three exons (shown as small solid arrows) separated by two introns. The genes are located on the same chromosome but are transcribed in opposite directions and separated by an intergenic region (IGR). The IGR length varies across species. The preprohormones contain a signal peptide (SP), Avp or Oxt, neurophysin (NP), and a glycopeptide (GP) in the case of Avp. Protein processing signals are represented with thick lines. Cysteine residues form a disulfide bond to create a cyclic six amino acid ring in both peptides. Seven out of nine amino acids are common and two amino acids (bold) are different between Avp and Oxt.

Figure 2

Distinct distributions of Avpr1a at two levels within the mouse brain. Receptor autoradiography was performed as described (Young et al., 2000) using an ¹²⁵I-labeled ligand. Abbreviations: CG, central grey; CP, caudate-putamen; Ctx, neocortex; H, hippocampal formation; LS, lateral septum; MS, medial septum; Sum, supramammillary nuclei; VP, ventral pallidum; VTA, ventral tegmental area.

Figure 3

Maternal aggression is much lower in Avpr1b KO mice compared to heterozygous (HET) and wildtype mice. *, p<0.05. Adapted from Wersinger et al. (2007a).

Figure 4

Pregnancy block (Bruce effect) is normal in Avpr1a KO mice but abnormal in different ways in Avpr1b and Oxt KO mice. As expected from the severe deficit in social recognition, Oxt KO females cannot remember their mates (A) and hence do not remain pregnant. In contrast, Avpr1b KO mice do not distinguish between their mates (A) and strange males (B) and “accept” either (B). Adapted from Wersinger et al. (2007c).

Figure 5

Hypothesized roles of the vasopressin 1a receptor (Avpr1a) and the vasopressin 1b receptor (Avpr1b) in the regulation of social behavior. Absence of the Avpr1a results in impaired olfaction, suggestive that the Avpr1a may be important to responses to chemosensory input (Wersinger et al., 2007b). On the other hand, absence of the Avpr1b results in reduced aggression and impaired social memory in the absence of olfactory deficits (Wersinger et al., 2004; Wersinger et al., 2007a). As the Avpr1b is found predominantly within the CA2 pyramidal neurons of the hippocampus, it has been proposed to be involved in the evaluation of accessory olfactory chemosensory cues (i.e., associating the cue with the behavioral context) (Young et al., 2006).