The neurobiology of pair bonding.

“Similar patterns of activity occur when mothers view images of their own children, suggesting some overlap between the neural mechanisms of maternal attachment and those of romantic lov”

“The release of oxytocin also occurs within the brain and modulates many aspects of behaviors including but not limited to maternal care [3–9], female sexual behavior [10–12], male sexual behavior [10, 13, 14], pair/social bonding [15] [16, 17], aggression [18–20], anxiety [21], and fear [22, 23].”

“Thus, songbird species would be similar to vole species [101] in that there are species differences in brain region-specific expression of hormone receptors that correlate with species differences in behaviour, monogamy-related in voles and singing-related in songbirds [101].”

“Indeed they are well known for their roles in social behavior, pairbonding, and mating systems (Young and Wang, 2004; Carter et al., 2008; Insel, 2010), including in humans (Heinrichs et al.”

“Thus, we explored the behavioral effects of intracerebroventricular (ICV) infusion of oxytocin (OXT), a nonapeptide that has been shown to facilitate many social behaviors, both in rodents (social memory [50], social preference [51], pair bonding [52], maternal care and maternal”

“…aesthetic experiences remind us of our humanness — our profound social attachments and loving dependencies, our massive social inter-relatedness to other people, feelings that are partly created by endogenous brain opioids and oxytocin (Nelson & Panksepp, 1998; Panksepp, 1981; Young & Wang, 2004).”

“The monogamous prairie vole expresses higher levels of V1aR in the VP and LS compared to other, non-monogamous, vole species, suggesting that this difference in receptor density may contribute to the differences in social behavior between vole species (16, 74, 75).”

“The physiological systems responsible for this attachmentspecific stress response include the dopamine system,(6) the opioid system,(15,16) and the oxytocin system.(17,18) The dopamine system is important in the experience of motivation to seek our rewards, both wanting to and, quite literally, moving toward a desired…”

“Use of transcription predictor assays suggests this might be due to alterations of gene expression in these different brain regions [53].”

“In rodents, OT is highly involved in social interaction, social recognition, pair bonding, and maternal behavior [8,15,17,18,19,22,25,30].”

“Evolved apparently to promote bonds between mothers and their offspring, various species have co-opted the mechanism to promote bonds, both between pair partners and between friends (Young and Wang 2004).”

“2003; Young and Wang, 2004 ) and in recognition of familiar individuals (Lim et al., 2005; Winslow and Insel, 2004; van Wimersma Greidanus and Maigret, 1996).”

“One could hypothesize that this OTR-D2R interaction is involved in partner preference, which depends on both OT and dopamine (Young & Wang 2004).”

“In contrast, the regional expression of OXY receptors is highly variable and explains differences in social attachment within and between species (Young and Wang, 2004).”

“Most of the behavioral effects of VP are mediated by the V1a subtype of VP receptors (Young and Wang, 2004), which may alter arousal or anxiety; between-species variation may thus result from species differences in coping strategies or stress re- sponses.”

“(Young and Wang, 2004), maternal care (Blanchard et al.”

“In sexual pair-bonds, partners develop selective preferences for each other, cooperate with each other to raise offspring, and in general, form a bond that indicates psychological ‘closeness’ (Young and Wang, 2004).”

“Centrally released OT, a major source of which is the paraventricular nucleus (PVN) of the hypothalamus, has been implicated in a number of mnemonic and social processes including reproductive and parental behaviors, the formation of social bonds, the management of stressful experiences, and trust in social interactio…”

“…et al., 2010), heterochronic shifts of " clocks " of cell specification with respect to the establishment of precursor pools to change neuron proportions (Finlay, 2008; Dyer et al., 2009), and extended or limited receptor distributions altering motivational strengths (Young and Wang, 2004).”

“, [76–79]).”

“The most characterized link between the oxytocinergic and the dopaminergic systems stems from the fact that OT-mediated social affiliative behaviours are also linked to key alterations in the dopaminergic reward system (Young and Wang, 2004; Skuse and Gallagher, 2009).”

“essential for the expression of many female social behaviors [47,48], clearly these neuropeptides influence social behavior in both sexes.”

“…terminalis (BNST; OTR), and ventral pallidum (VPall; V1aR), but lower receptor density in the lateral septum (LS; V1aR) than their non-monogamous congeners (Insel et al., 1994; Insel & Shapiro, 1992; Lim & Young, 2004; Smeltzer, Curtis, Aragona, & Wang, 2006; Wang et al., 1997; Young et al., 1997).”

“Peptides in this family exert considerable influence on vertebrate social behavior (Goodson and Adkins-Regan, 1999; Young and Wang, 2004), with evidence in white-crowned sparrows for a stimulatory role in song production (Maney et al., 1997) and for vasotocin binding sites in song related brain…”

“Recent findings indicate that oxytocin, a neuropeptide critical for pair bonding within some species (Winslow, 1993; Young and Wang, 2004), has a role in mediating dog behavior toward humans (Odendaal and Meintjes, 2003; Romero et al. , 2014; Nagasawa et al. , 2015; Thielke and Udell, in press).”

“…focused on length variations in the upstream 5′-region of the Avpr1a gene, finding that individuals with longer Avpr1a alleles show increased sociability (Hammock et al., 2005; Hammock and Young, 2005; Knafo et al., 2008; Meyer-Lindenberg et al., 2009; Walum et al., 2008; Young and Wang, 2004).”

“Administration of these agents can induce the pair bond in the absence of mating and antagonizing dopamine-2 (D2) receptors can block the formation of a pair bond (Young and Wang, 2004).”

“Together, these brain areas mediate naturally rewarding behaviors including feeding [2,3,4,5], drinking [6], maternal behavior [7], social bonding [8,9] and sexual behavior [10,11,12,13,14].”

“All these limbic and hypothalamic brain areas appear to be crucial components for the execution of socio-affiliative behaviours in rodents and for modulating neural reward pathways as a consequence of social interaction (Aragona et al., 2006; Edwards and Self, 2006; Keverne and Curley, 2004; Young and Wang, 2004).”

“For instance, the strong impact of oxytocin on female social behavior (Young and Wang, 2004), and the disproportionately high risk of men for social disorders (Baron-Cohen, 2002), suggest sex dependent genotype effects (Tost et al.”

“Most notably, the numerous positive affective responses that sexual intercourse produces (Carmichael et al., 1987; Sbarra & Hazan, 2008; Young & Wang, 2004) should automatically become more strongly associated with the partner as the frequency of sex increases.”

“, 2000), and activation of both D2 dopamine and OT receptors in the NAc and prelimbic cortex, is necessary for partner preference formation (Gingrich et al., 2000; Liu and Wang, 2003; Young and Wang, 2004; Young et al., 2001).”

“It also should be noted that central dopamine interacts with the neuropeptides oxytocin (through co-localization of receptors in the nucleus accumbens), and vasopressin (via projections from the nucleus accumbens to the ventral pallidum) to modulate vole social interactions [94].”

“…vole, but not in mice, rats, montane, and meadow voles, which do not form pair bonds, was the NAc (Bielsky & Young, 2004; Insel et al., 1991; Ross et al., 2009; Young & Wang, 2004), raising the possibility that oxytocin and DA might work together to enable species specific pair bonding behaviors.”

“…neuromodulator in a variety of species to influence complex social behaviors, including social bonding (A. S. Smith, Ågmo, Birnie, & French, 2010; Young & Wang, 2004), social memory (Dantzer, Bluthé, Koob, & Le Moal, 1987; Ferguson, Aldag, Insel, & Young, 2001; Ferguson et al., 2000),…”

“Indeed, this finding fits with the crucial function of OT as a female hormone in labor, bonding and parenting both in human- [54], [4] and nonhuman mammals [55] and is in agreement with recent experimental evidence pointing to the sex-dimorphic effects of OT nasal spray in humans [19], [45] [56], [57].”

“, 2008) and fail to model important aspects of human social interactions (Young and Wang, 2004).”

“Amongmammals, recent examples include the study of pair-bonds (Young and Wang, 2004; Ophir et al., 2007), non-sexual bonds (Beery and Zucker, 2010), elaborate vocalizations (Blondel and Phelps, 2009; Crino et al.”

“An important emerging concept is that empathic abilities may strongly rely on the neurobiology of social attachment or bonding, which has been extensively studied in animals (Insel, 1997; Young and Wang, 2004) and, more recently, in humans (Bowlby, 1988; Moll et al.”

“…more affected by negative reproductive outcomes of casual sex (e.g., unwanted pregnancy) and more susceptible to forming attachment bonds following casual sex (de Graaf & Sandfort, 2004; Townsend & Wasserman, 2011), perhaps due to differential effects of oxytocin (Young & Wang, 2004).”

“Oxytocin acts as a neuropeptide in the brain, and has been implicated in a wide variety of social processes and behaviors, particularly those related to affiliation and bonding (Carter et al., 1992; Young and Wang, 2004; Feldman, 2012b).”

“In the last two decades, neurobiological investigations of parental behavior (Numan and Insel, 2003) and partner preference formation between mates (Young and Wang, 2004; Lim and Young, 2006) have yielded important insights into these behaviors.”

“For example, AVP acts in various brain regions to alter vertebrate social communication (Goodson and Bass, 2001; Kelly and Goodson, 2013), maternal care (Bosch and Neumann, 2008), pair bonding (Carter et al., 1995; Jarcho et al., 2011; Young and Wang, 2004), and social recognition (Dantzer et al.”

“These include the welldocumented vole species clade, in which the actions of neuropeptides like oxytocin and vasopressin are known to regulate social pair bonding behavior via actions in the ventral forebrain (Young and Wang, 2004).”

“Conversely, similar neuromodulatory actions in disparate species might underlie independent evolution of analogous behaviors (Young and Wang, 2004).”

“it increases the release of oxytocin, which in turn increases dopamine transmission in the nucleus accumbens, hence promoting social bonding.(15,16) In parallel, an increase in oxytocin in the hypothalamus is responsible for the dampening of the neuroendocrine responses.”

“Comparative studies of these species, such as the monogamous prairie (Microtus ochrogaster) and pine (Microtus pinetorum) voles in contrast to their promiscuous sister species, the meadow (Microtus pennsylvanicus) and montane (Microtus montanus) voles, have shed much light on several neurotransmitter systems that modu…”

“Like VIP (Kingsbury et al. 2013), oxytocin modulates grouping and affiliative behavior (Young and Wang 2004; Goodson et al. 2009b; Goodson and Kingsbury 2011; Young et al. 2011).”

“If orgasm led to endocrine responses propitious for bonding (CoriaAvila, Herrera-Covarrubias, Ismail, & Pfaus, 2016; Young and Wang, 2004), then the ancestral female's orgasm would have increased her affiliation to the mate, and if the activities resulted in coitus and the male's orgasm aswell, the…”

“For example, the AVP signaling system underlies pair bonding more prominently in male prairie voles, while in female voles OT signaling pathways play a more important role (Young and Wang, 2004).”

“While there is general agreement that the action of vasopressin in the VPall and oxytocin in the NAcc are both important in monogamous pairbonding [65], what role oxytocin/OTR plays in male NAcc and vasopressin/V1aR plays in female VPall remains unclear.”

“, 2008) and also in the regulation of emotional and social behaviour in both males and females (Dantzer et al., 1987; Young and Wang, 2004; Heinrichs and Domes, 2008; Neumann, 2008; Skuse and Gallagher, 2009).”

“For example, only about 5% of mammals are monogamous, exhibiting strong social bonds after mating (52, 53).”

“Dopamine D2 receptors and oxytocin acting in the nucleus accumbens shell, but not the core, play a vital role in the formation of pair bonds in monogamous voles, while D1-like receptors are important for pair bond maintenance (Aragona et al., 2006; Young & Wang, 2004).”

“An alternative animal model relevant to ASD is the meadow vole (Microtus pennsylvanicus), which, despite being closely related to the prairie vole, is relatively asocial and does not typically display partner preferences, in part because of a lack of OT receptors in the NAcc (26).”

“This family of neuropeptide hor- mones is implicated in diverse complex social behaviors, including affiliative behavior (parental care, pair bonding, social recognition), aggression, fear behavior, and reproduction (Carter, 2002; Young and Wang, 2004).”

“The AVP receptors, V1a and V1b, are distributed in the prefrontal cortex, hippocampus, amygdala, and various other regions of the brain and regulate anxiety and pair bonding behavior (Young and Wang, 2004).”

“ORIGINAL RESEARCH ARTICLE published: 01 April 2013 doi: 10.3389/fnins.2013.00045 Imaging oxytocin × dopamine interactions: an epistasis effect of CD38 and COMT gene variants influences the impact of oxytocin on amygdala activation to social stimuli”

“Our findings support the broader hypothesis that sexual activity within a relationship—even that which does not result in conception—serves a variety of functions that affect reproductive health, from improving pair bonds (35) and improving relationship satisfaction across the lifespan (36) to engaging endocrine and i…”

“The prairie vole (Microtus ochrogaster) is a monogamous rodent species showing enduring pair bonding between mates, biparental care, and the consoling behavior toward a distressed partner (Young and Wang, 2004; Aragona et al., 2006; Gobrogge et al., 2009; Young et al., 2011; Johnson and Young, 2015; Burkett et al., 20…”

“For instance, OXTR signaling in the nucleus accumbens (NAc) and prelimbic cortex (PLC) is critical for pair bonding in monogamous prairie voles, and monogamous and polygamous vole species differ in OXTR expression in these regions (L. J. Young et al., 1996, 2001; L. J. Young & Wang, 2004).”

“…(also referred to as companionate love or pair bonding in the human and animal literature, respectively) reflects the comforting feeling of emotional bonding with another individual (e.g., see De Boer, Van Buel, & Ter Horst, 2011; Fisher, 1998, 2000; Sprecher & Regan, 1998; Young & Wang, 2004).”

“36 Both OT and VP are involved in the regulation of partner preference and facilitate the preference for familiar ones, although OT appears more important.”

“Additionally, in monogamous rodents, both of these neuropeptide systems play a role in long-term social bonds [Williams, Carter, & Insel, 1992; Winslow et al., 1993; Young & Wang, 2004].”

“Comparative studies between monogamous and promiscuous vole species have provided some of the first insights into the neural mechanisms regulating pair bonds, to be reviewed further later (293,296).”

“Pair bond formation is routinely studied in the laboratory by using a partner preference test [60,61] and such studies have provided excellent insight into the neural regulation of pair bonding [62].”