The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies

Abstract

The formation and maintenance of social bonds in adulthood is an essential component of human health. However studies investigating the underlying neurobiology of such behaviors have been scarce. Microtine rodents offer a unique comparative animal model to explore the neural processes responsible for pair bonding and its associated behaviors. Studies using monogamous prairie voles and other related species have recently offered insight into the neuroanatomical, neurobiological, and neurochemical underpinnings of social attachment. In this review, we will discuss the utility of the microtine rodents in comparative studies by exploring their natural history and social behavior in the laboratory. We will then summarize the data implicating vasopressin, oxytocin, and dopamine in the regulation of pair bonding. Finally, we will discuss the ways in which these neurochemical systems may interact to mediate this complex behavior.

Figure 1. Comparison of prairie and meadow vole social behavior

(A) Photos showing species differences in affiliative behavior of conspecific sexually naive prairie (top) and meadow (bottom) voles. (B) Prairie voles show bi-parental care of offspring whereas meadow voles show maternal care. (C) After 24 hours of mating, prairie, but not meadow, voles develop a partner preference and spend significantly more time in side-by-side contact with their partner than a conspecific stranger during a three hour choice test. (D) Sexually naive male prairie voles (Naive) show little aggression, whereas pair bonded males display intense aggression toward conspecific male and female strangers, but not toward their partner (selective aggression). (Adapted from McGuire et al., 1984; McGuire et al., 1986; Winslow et al., 1993; Aragona et al., 2003; Lim et al., 2004b; Aragona et al., 2006; Gobrogge et al., 2007).

Figure 2. AVP and OT involvement in pair bonding in prairie voles

(A) Photomicrographs showing that monogamous prairie voles have higher V1aR labeling densities in the ventral palladium (VP) and lower densities in the lateral septum (LS) than (B) promiscuous montane voles. (C) Prairie voles have higher densities of OTR labeling in the nucleus accumbens (NAcc) and prefrontal cortex (PFC) than (D) montane voles. (E) Mating induced partner preferences in male prairie voles that received injections of cerebrospinal fluid (CSF) into the lateral ventricle but not in males that received injections of a V1aR antagonist (V1aR ant). Infusion of AVP into the lateral ventricle induced partner preferences without mating. (F) Similarly, central administration of an OTR antagonist (OTR ant) blocked mating induced partner preferences in female prairie voles, whereas OT infusion into the lateral ventricle induced partner preferences without mating. (Adapted from Winslow et al., 1993; Insel et al., 1995a; Cho et al., 1999).

Figure 3. V1aR distribution may contribute to social organization

Photomicrographs showing V1aR labeling in the ventral pallidum (VP) of prairie (A) and meadow (B) voles. (C) Meadow voles transgenic for the prairie vole V1aR gene (V1aR-VP) showed an increased density of V1aR labeling in the VP. (D) Twenty-four hours of mating induced partner preferences in the V1aR-VP transgenic, but not control, meadow voles. (Adapted from Lim et al., 2004b).

Figure 4. DA regulation of pair bonding in male prairie voles

(A) Peripheral injection of haloperidol (Halo), a nonspecific DA receptor antagonist, blocked partner preference formation following 24 hours of mating. (B) Pharmacological blockade of D2Rs (D2 ant) in the nucleus accumbens (NAcc) prevented mating induced partner preferences, whereas administration of a D2R agonist (D2 ago) induced partner preferences without mating, indicating the importance of D2R activation in partner preference formation. (C) Intra-NAcc injection of a D1R agonist (D1 ago) blocked partner preference formation following 24 hours of mating. (D) Photomicrographs showing increased D1-like receptor binding in the NAcc of male prairie voles that were pair bonded for two weeks (Paired) in comparison to sexually naive males (Naive). (E) Two weeks of pair bonding induced a significant increase in the density of D1-like, but not D2-like, receptors in the NAcc of male prairie voles. (F) Pair bonded male prairie voles displayed a high level of aggression toward a stranger female (CSF + Stranger), but not toward their own familiar partner (CSF + Partner). Intra-NAcc blockade of D1-like receptors (D1 Ant + Stranger), but not D2-like receptors (D2 Ant + Stranger) abolished selective aggression toward a stranger female. (Adapted from Wang et al., 1999; Aragona et al., 2003; Young et al., 2004; Aragona et al., 2006).