The neurobiology of pair bonding: insights from a socially monogamous rodent

Abstract

The formation of enduring relationships between adult mates (i.e., pair bonds) is an integral aspect of human social behavior and has been implicated in both physical and psychological health. However, due to the inherent complexity of these bonds and the relative rarity with which they are formed in other mammalian species, we know surprisingly little about their underlying neurobiology. Over the past few decades, the prairie vole (Microtus ochrogaster) has emerged as an animal model of pair bonding. Research in this socially monogamous rodent has provided valuable insight into the neurobiological mechanisms that regulate pair bonding behaviors. Here, we review these studies and discuss the neural regulation of three behaviors inherent to pair bonding: the formation of partner preferences, the subsequent development of selective aggression toward unfamiliar conspecifics, and the bi-parental care of young. We focus on the role of vasopressin, oxytocin, and dopamine in the regulation of these behaviors, but also discuss the involvement of other neuropeptides, neurotransmitters, and hormones. These studies may not only contribute to the understanding of pair bonding in our own species, but may also offer insight into the underlying causes of social deficits noted in several mental health disorders.

Figure 1

Laboratory characterization of behaviors associated with pair bonding. (A) Photo illustrates a male and female prairie vole displaying side-by-side contact. (B) Three-chamber apparatus used to test for partner preferences. Three identical cages are connected by hollow tubes with light sensors allowing for automated analysis of the subject’s movements throughout the apparatus. Social behaviors between the subject (white) and the partner (black) and stranger (gray) during the three hour test are recorded and subsequently scored. Duration of side-by-side contact is the primary behavior of interest. (C) In both male and female prairie voles, 6 hours of cohabitation without mating does not result in partner preference formation, as the subject spends equal amounts of time in contact with the partner as with the stranger. In contrast, 24 hours of cohabitation with mating leads to the formation of partner preferences, as indicated by the subject spending significantly more time in side-by-side contact with the partner than the stranger during the 3 hour partner preference test. (D) Photo depicts a pair-bonded male prairie vole (left) displaying attack behavior toward an unfamiliar female. Sexually naïve (Naïve) males do not exhibit aggressive behavior toward a stranger, however males paired with a female for two weeks (Paired) demonstrate robust aggression toward stranger male and female conspecifics but not toward familiar female partners. (E) Photo shows a male and female prairie vole sharing a natal nest and contacting offspring. Male and female prairie vole parents spend equal amounts of time in the natal nest. Bars indicate means ± standard error of the mean. Bars with different Greek letters differ significantly from each other. *: p < 0.05. Adapted from [10, 99, 222, 231].

Figure 2

Vasopressin (AVP) and oxytocin (OT) regulation of partner preference formation. (A) Species differences in vasopressin receptor (V1aR) binding in the ventral pallidum (VP) of prairie and montane voles. Higher densities of receptors are indicated by more red coloration. (B) Site-specific manipulation of AVP neurotransmission in the lateral septum (LS) of male prairie voles. Data demonstrate that after 6 hours of non-sexual cohabitation with a female (Cohab), control males given LS injections of vehicle (cerebrospinalfluid; CSF) do not display partner preferences. However, AVP infusion into the LS induces partner preferences. Following 24 hours of cohabitation with mating (Mated), CSF treated control males display partner preferences. However, blockade of V1aRs, via infusion of a V1aR antagonist (V1aR Ant) into the LS inhibits the formation of mating-induced partner preferences. (C) Male prairie voles overexpressing the V1aR gene (AAV-V1aR) in the ventral pallidum display partner preferences after 17 hours of non-sexual cohabitation with females, whereas control males do not. (D) Species differences in oxytocin receptor (OTR) binding in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc) of prairie and montane voles. (E) Site-specific manipulation of OT neurotransmission in the NAcc of female prairie voles. After 6 hours of non-sexual cohabitation with a male (Cohab), female prairie voles infused with OT in the NAcc display partner preferences, whereas control females infused with CSF do not. After 24 hours of cohabitation with mating (Mated), control females infused with CSF form partner preferences. However, intra-NAcc blockade of OTRs, via infusion of an OTR antagonist (OT Ant), inhibits the formation of mating-induced partner preferences. (F) Female prairie voles overexpressing the OTR (AAV-OTR) in the NAcc form partner preferences after less than 24 hours of mating and cohabitation with a male whereas control females do not. Bars indicate means ± standard error of the mean. *: p < 0.05. Adapted from [149, 150, 183, 188].

Figure 3

Dopamine (DA) in the nucleus accumbens (NAcc) regulates partner preference formation in prairie voles. (A) Cartoon illustrates the mesolimbic DA circuit. DA-ergic cells in the ventral tegmental area (VTA) project to the NAcc and prefrontal cortex (PFC), as well as other forebrain regions. Released DA binds to one of two DA receptor subtypes, D1-like receptors (D1R) and D2-like receptors (D2R), which are both present in the NAcc of prairie voles, as shown in the photoimage. (B) Activation of D2Rs via injection of a D2R agonist (D2 Ago) into the NAcc of males induces partner preferences after 6 hours of non-sexual cohabitation (Cohab). Twenty-four hours of mating (Mated) induces partner preferences in control males that receive intra-NAcc injection of CSF. However, mating-induced partner preference formation was inhibited by intra-NAcc blockade of D2Rs (via injection of a D2R antagonist (D2 Ant)) or activation of NAcc D1Rs (via injection of a D1R agonist (D1 Ago). (C) Cartoon illustrating the effects of D1R and D2R activation on cAMP intracellular signaling. D1Rs are coupled to stimulatory G-proteins (Gα_s/olf) and D2Rs are coupled to inhibitory G-proteins (Gα_i/o). D1R activation increases adenylate cyclase (AC) activity, leading to an increase in the production of cAMP and the activation of PKA. D2R activation leads to the inhibition of AC, through the effects of the alpha subunit of Gα_i/o, decreasing cAMP production and PKA activity. (D) Pharmacologically decreasing PKA activity (↓ PKA) in the NAcc induces partner preference formation in male prairie voles after 6 hours of non-sexual cohabitation (Cohab). Pharmacologically increasing NAcc PKA activity (↑ PKA) during 24 hours of mating (Mated) blocks mating-induced partner preferences. Bars indicate means ± standard error of the mean. *: p < 0.05. Adapted from [–9, 238].

Figure 4

Vasopressin (AVP) and dopamine (DA) involvement in selective aggression in male prairie voles. (A) Photomicrograph shows AVP-immunoreactive (AVP-ir) cell bodies and fibers (brown cytoplasmic staining), Fos-immunoreactive (Fos-ir) staining (dark nuclear staining), or both (insert) in the anterior hypothalamus (AH). (B) Males pair-bonded with a female for two weeks displaying aggression toward either male or female strangers, have a significantly higher density of AVP-ir/Fos-ir double labeled cells in the AH compared to males re-exposed to their partner or not exposed to any conspecific (control). (C) AH-AVP release is higher in pair-bonded males that are exposed to a stranger female than those that are re-exposed to their partner. (D) Males paired with a female for two weeks (Paired) have higher densities of vasopressin receptors (V1aRs) in the AH than males that are sexually naïve (Naïve). (E) Sexually naïve males (Naïve) given intra-AH injections of AVP display significantly more aggression than males treated with CSF, and this AVP-induced aggression is blocked by concurrent administration of AVP with a V1aR antagonist (V1aR Ant). Pair-bonded males (Paired) display robust aggression toward novel females and this behavior is significantly decreased by intra-AH injection of a V1aR antagonist. (F) Sexually naïve males injected in the AH with an adeno-associated virus expressing the V1aR gene (AAV-V1aR) display significantly more aggression toward stranger females than control males. (G) Pair-bonded males (Paired) have higher densities of D1Rs in the NAcc than sexually naïve males (Naïve). (H) These differences in D1R density between paired and naïve males are significant, however no group differences are found in NAcc D2R density. (I) Pair-bonded males display aggression toward a stranger female, but not their partner, and these effects are blocked by the infusion of a D1R antagonist (D1R Ant), but not D2R antagonist (D2R Ant), into the NAcc. Bars indicate means ± standard error of the mean. Bars with different Greek letters differ significantly from each other. *: p < 0.05. Adapted from [8, 99, 100].