The role of the vasopressin 1b receptor in aggression and other social behaviours
Introduction
Originally described in pituitary (Antoni, 1984; Jard et al., 1986; Arsenijevic et al., 1994) and subsequently cloned (Lolait et al., 1995), the vasopressin (Avp) 1b receptor (Avpr1b) is found in several brain areas and peripheral tissues (Arsenijevic et al., 1994; Lolait et al., 1995; Young et al., 2006). Within the anterior pituitary the Avpr1b facilitates the release of adrenocorticotropic hormone (ACTH) from the corticotropes (Jard et al., 1987; Antoni, 1993), thus helping mediate the effects of Avp on the hypothalamic–pituitary–adrenal axis, i.e., the mammalian stress axis (Volpi et al., 2004). In the periphery, Avpr1b mRNA is found in tissues including kidney, thymus, heart, lung, spleen, uterus and breast (Lolait et al., 1995), although its role in these tissues remains unclear. It is only relatively recently that Avpr1b transcripts as well as Avpr1b immunoreactive cell bodies have been found in the rat brain, including in the olfactory bulb, piriform cortical layer II, septum, cerebral cortex, hippocampus, paraventricular nucleus, suprachiasmatic nucleus, cerebellum and red nucleus (Lolait et al., 1995; Saito et al., 1995; Vaccari et al., 1998; Hernando et al., 2001; Stemmelin et al., 2005). It should be noted, however, that Avpr1b distribution has not been mapped by receptor autoradiography due to the lack of a specific radiolabeled ligand. A recent study using in situ hybridization histochemistry with more specific probes on mouse, rat and human tissues found prominent Avpr1b expression in the hippocampal CA2 field pyramidal neurons (Young et al., 2006).
The Avpr1b knockout mouse (Avpr1b−⧸−) was developed prior to any Avpr1b-specific pharmacology and has provided critical insights into the roles of the Avpr1b in the mouse, and possibly other species. While pharmacologically ‘clean’ compounds have continued to be somewhat elusive, the available pharmacological data are consistent with our observations in Avpr1b−⧸− mice (Blanchard et al., 2005; Griebel et al., 2005). Originally described by Wersinger et al., 2002, Wersinger et al., 2004, Avpr1b−/− mice, compared to wildtype controls, have reduced aggression and investigation of social cues as well as mild deficits in social memory. Taken together, these findings suggest that absence of the Avpr1b gene results in impairments that affect social behaviours more than other behaviours. The Avpr1b is also important for normal responses to some acute and chronic stressors (for review see Serradeil-Le Gal et al., 2005). While genetic disruption of the Avpr1b fails to affect measures of anxiety-like behaviour, depression-like behaviour (Wersinger et al., 2002; Caldwell et al., 2006) or the corticosterone response to acute restraint stress (Lolait et al., 2007a); its disruption attenuates the corticosterone response to forced swim, acute insulin treatment, acute immune stress and ethanol intoxication (Tanoue et al., 2004; Lolait et al., 2007a, Lolait et al., 2007b). Avpr1b−⧸− mice also demonstrate a blunted ACTH response under chronic stress conditions (Lolait et al., 2007a) and pharmacological blockage of Avpr1b receptors reduces ACTH secretion (Serradeil-Le Gal et al., 2002). While the role of the Avpr1b in the mediation of the stress axis and other physiological responses (Oshikawa et al., 2004; Itoh et al., 2006; Fujiwara et al., 2007) are interesting and active areas of research, this chapter will focus on the contributions of the Avpr1b to the regulation of social behaviour.
Section snippets
Avpr1b and aggression
The Avpr1b gene is essential for the normal expression of aggressive behaviour. Furthermore, the Avpr1b is critical for the initiation of offensive behaviour, but only toward a conspecific. Avpr1b−⧸− mice have longer attack latencies and fewer attacks toward an intruder compared to wildtype controls in a resident–intruder test (Wersinger et al., 2002, Wersinger et al., 2006) (Fig. 1). Disruption of the Avpr1b does not, however, result in a global deficit in all aggressive behaviour. Several
Avpr1b and social memory
The ability of an organism to recognize individuals or social situations is critical in the determination of what behaviours will be displayed. In mice, one way to test social memory is to use a social recognition test in which, based on sniff time, a mouse demonstrates the ability to discriminate familiar from novel individuals. Avp is important for individual recognition, in particular through the androgen-dependent vasopressinergic projections from the medial amygdala and bed nucleus of the
Avpr1b and social motivation
To characterize more fully the social deficits found in Avpr1b−/− mice, we tested their motivation to interact with socially salient stimuli. Described in Wersinger et al. (2004), Avpr1b−/− mice and wildtype mice were tested for bedding preferences. The mice were given three different preference tests: (1) female-soiled bedding versus male-soiled bedding; (2) female-soiled bedding versus clean bedding; (3) male-soiled bedding versus clean bedding. During each of these tests, the percent of
Conclusions
Over the past several years, we have laid the foundation necessary to study the role of the Avpr1b in the regulation of social behaviour. We have demonstrated that the deficits in behaviour all share one common feature — modulation by accessory olfactory information. Mapping the Avpr1b in the mouse was challenging and until recently (Young et al., 2006) we were not able to localize the receptor's expression. While there is much work to be done to understand the role of the Avpr1b in the
Abbreviations
- ACTH
adrenocorticotropic hormone
- Avp
vasopressin
- Avpr1a
vasopressin 1a receptor
- Avpr1b
vasopressin 1b receptor
- Avpr1b−/−
vasopressin 1b receptor knockout
Acknowledgement
This work was supported by the NIMH Intramural Research Program (Z01-MH-002498-17).
References (51)
Vasopressinergic control of pituitary adrenocorticotropin secretion comes of age
Front. Neuroendocrinol.
(1993)- et al.
Input-output relations in the entorhinal cortex–dentate–hippocampal system: evidence for a non-linear transfer of signals
Neuroscience
(2006) - et al.
Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female Avpr1a receptor knockout mice
Behav. Brain Res.
(2005) - et al.
AVP V(1b) selective antagonist SSR149415 blocks aggressive behaviors in hamsters
Pharmacol. Biochem. Behav.
(2005) - et al.
Gonadal steroids influence the involvement of arginine vasopressin in social recognition in mice
Psychoneuroendocrinology
(1993) - et al.
Androgen-dependent vasopressinergic neurons are involved in social recognition in rats
Brain Res.
(1990) - et al.
The acute intoxicating effects of ethanol are not dependent on the vasopressin 1a or 1b receptors
Neuropeptides
(2006) - et al.
Gonadal hormone actions on the morphology of the vasopressinergic innervation of the adult rat brain
Brain Res.
(1984) - et al.
Effects of hippocampal lesions on cardiovascular, adrenocortical and behavioral response patterns in mice
Physiol. Behav.
(1977) - et al.
Microdialysis administration of vasopressin into the septum improves social recognition in Brattleboro rats
Physiol. Behav.
(1994)
Neurohypophyseal hormone receptor systems in brain and periphery
Prog. Brain Res.
Gonadal steroids influence neurophysin II distribution in the forebrain of normal and mutant mice
Neuroscience
Molecular cloning and characterization of rat Avpr1b vasopressin receptor: evidence for its expression in extra-pituitary tissues
Biochem. Biophys. Res. Commun.
Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task
Horm. Behav.
The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy
Neuroscience
Novel ligand specificity of pituitary vasopressin receptors in the rat
Neuroendocrinology
Vasopressin-binding sites in the pig pituitary gland: competition by novel vasopressin antagonists suggests the existence of an unusual receptor subtype in the anterior lobe
J. Endocrinol.
Involvement of the vomeronasal organ and prolactin in pheromonal induction of delayed implantation in mice
J. Reprod. Fertil.
Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin Avpr1a receptor knockout mice
Neuropsychopharmacology
An exteroceptive block to pregnancy in the mouse
Nature
Role of olfactory sense in pregnancy block by strange males
Science
Correlations between granule cell dispersion, mossy fiber sprouting, and hippocampal cell loss in temporal lobe epilepsy
Epilepsia
Hippocampal pathology in patients with intractable seizures and temporal lobe masses
J. Neurosurg.
Mutual regulation of vasopressin- and oxytocin-induced glucagon secretion in Avpr1b vasopressin receptor knockout mice
J. Endocrinol.
Non-peptide vasopressin Avpr1b receptor antagonists as potential drugs for the treatment of stress-related disorders
Curr. Pharm. Des.
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