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”

“Interestingly, these social relationships both promote and are regulated by the oxytocin system (reviewed in Young and Wang, 2004; Young et al., 2005).”

“The initial hype and promise generated from preclinical models [Young & Wang, 2004] and a prominent paper in Nature [Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005] spurred a flurry of clinical studies, all focused on the treatment implications for social impairments across a variety of…”

“Based on ecological (Emlen and Oring, 1977) and neuroanatomical (Young and Wang, 2004) theory, we expect that across taxa, the expression of neuropeptide receptors underlying mating systems (e.”

“…suggested by sitespecific VP manipulations within the ventral pallidum and LS, the BSTm neurons appear to be important mediators of affiliative behaviors such as bonding, non-sexual contact, and social recognition (reviews: Landgraf and Neumann, 2004; Wang and Aragona, 2004; Young and Wang, 2004).”

“These previous studies argued that peptide systems are necessary for social recognition, while DA transmission is important for reward processing (Young and Wang, 2004; Johnson and Young, 2015).”

“Fostering a conditioned link between sexual reward and a specific partner, oxytocin is thus clearly implicated in the formation of pair bonds (e.g., Young & Wang, 2004).”

“, 1991), and oxytocin has been implicated in modulating olfactory memory in the limbic system of rodents (Young and Wang, 2004).”

“Additionally, research suggests that monogamous and polygamous rodents can be distinguished by patterns of OT receptor distributions across social and reward brain regions (Young and Wang, 2004).”

“DA has also been shown to regulate pair bonding in female prairie voles (Young and Wang, 2004).”

“Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love”

“…to increases in the activity of two neurotransmitter systems: oxytocin, which promotes feelings of trust, love, and affiliation, and endogenous opioids, such as endorphins, which decrease the experience of physical pain (Depue & MorroneStrupinsky, 2005; Sbarra & Hazan, 2008; Young & Wang, 2004).”

“Although several mechanisms have been proposed to regulate the formation of pair bonds, the neuropeptide arginine vasopressin has been proposed to be the primary mechanism involved in regulating pair bond formation and parental behavior in male prairie voles (Young and Wang, 2004).”

“Furthermore, the expression of OT receptors (OTR) within the caudate putamen (CP) and the NAcc is higher in the monogamous prairie vole compared to the non-monogamous montane vole (Microtus montanus) (Young and Wang, 2004).”

“, 2006) and elicits oxytocin release (Depue and Morrone-Strupinsky, 2005; Young and Wang, 2004), which in turn has been shown to reduce cortisol response to the TSST, in interaction with social support (Heinrichs et al.”

“, 2007) and adult heterosexual elationships in monogamous species (Wang and Aragona, 004; Young and Wang, 2004).”

“Given the potential of oxytocin as a treatment for disorders of social affiliation such as SZ and autism (Young and Wang, 2004; Hammock and Young, 2006; Meyer-Lindenberg et al., 2011), and the intranasal delivery route of oxytocin to olfactory pathways, abnormalities in the latter being a potential endophenotype in SZ…”

“The obvious choice in this initial study was dopamine, partly because it has been found to be critical for pair-bonding in voles (rodents) (Young and Wang, 2004; Mcgraw and Young, 2010), even if it does not act in isolation but as part of a critical”

“This emerging model organism has proven useful for investigating the neurobiological and genetic mechanisms underlying a variety of social phenomena, including bond formation (Carter et al., 1995; Young and Wang, 2004), bond maintenance (Aragona et al.”

“…dopaminergic system consists of the ventral tegmental area (VTA) projecting to many forebrain nuclei in what has been described as the reward system and is important for reinforcing learned 88 The Journal of Comparative Neurology | Research in Systems Neuroscience behavior (Young and Wang, 2004).”

“…striatum, dorsal raphe, and hypothalamus (Gingrich et al. 2000; Young et al. 2001; Leypold et al. 2002; Robinson et al. 2002; Liu and Wang 2003; Young and Wang 2004; Curtis and Wang 2005; Aragona et al. 2006; Lin et al. 2011; Robinson et al. 2011; Dölen et al. 2013; Yang et al. 2013;…”

“There are both individual and species differences in avpr1a expression and these have been associated with variation in pair bonding and other dimensions of social behavior in voles (Hammock et al., 2005, Hammock & Young, 2005, Hammock & Young, 2006, Young & Wang, 2004).”

“The consequences of various social stressors, including (but not limited to) social isolation, also have been investigated using prairie voles, which are rodents that display socially monogamous behaviors similar to humans, such as forming long-term social bonds and living in family groups (12,13).”

“Dopamine fluctuations in ventral forebrain can initiate locomotor sequences via modulating the input to spinal pattern generators (Grillner, 2003), and similarly, in prairie voles the coupling of forebrain dopamine and neuropeptide signaling is considered crucial for maintaining conditioned partner preferences via dow…”

“…forms monogamous sexual pair bonds and shows biparental care, suggests that OXT and AVP play a role in bonding between sexual partners (reviewed in Young & Wang, 2004): Monogamous prairie voles, compared to nonmonogamous species, have higher OXTreceptor and AVP-receptor densities (Insel &…”

“In fact, in prairie voles, OXT facilitates pair-bond formation through its interaction with dopamine release particularly in the nucleus accumbens (NAcc) [Young and Wang, 2004].”

“…binding and presynaptic OT elements in the mouse striatum would be useful, since OT transmission in the Acb is the focus of multiple studies on the neural basis of pair bonding (Young and Wang 2004), social reward mechanisms (Dölen et 2013) and addiction to drugs of abuse (Sarnyai and Kovács 1994).”

“The mates care for their pups bi-parentally and display selective aggression toward unfamiliar conspecifics, and the neural mechanisms underlying these behaviors are being rapidly elucidated (Aragona et al., 2006; Gobrogge et al., 2009; Johnson and Young, 2015; Walum and Young, 2018; Young et al., 2011; Young and Wang…”

“True individual recognition also allows the formation of individual-specific social bonds such as the mating bonds shown by the reproductive pairs of monogamous voles or gerbils [37,245,310].”

“Specifically, in the monogamous prairie vole, vasopressin receptor (V1aR) binding (concentration) is very dense in the ventral forebrain, in particular in the ventral pallidum which is a region associated with reward and motivation (Lim, Murphy & Young, 2004).”

“We examined c-fos expression in the NAcc, medial amygdala (mAMG), lateral septum (LS) and prefrontal cortex (PFC), all of which are forebrain areas previously implicated in social behavior in voles [1,10,20,31,34,35,52], and in the arcuate nucleus, an area not known to play a role in pair bonding.”

“These findings are also consistent with studies in rodents that have established roles for endogenous AVP in V1a-mediated behaviors such as social recognition, pair bonding, parental behavior, alloparental behavior, and nonsexual investigation (Young and Wang, 2004; Lim and Young, 2006; Carter et al., 2008; Veenema an…”

“Yet, differences between TL and AB fish in the expression levels of oxt and avp, which are involved in regulating social behaviour (Ebstein et al. 2012; Goodson 2008; Lukas & Neumann 2013; Young & Wang 2004), may already point to this possibility.”

“The neurobiology of pair bonding is outside of the scope of the present paper, and the reader is referred to an excellent previous review ( Young and Wang, 2004 ) as well as the paper by Lim and Young is this special issue of Hormones and Behavior for further information on this topic.”

“Interestingly, the DRD2 genetic association results can also be related to this phenotype, since pair bonding in monogamous rodents is partially linked to D2 receptors in nucleus accumbens and to the mesolimbic dopamine reward system [52].”

“…Winslow et al., 1993; Oldfield and Hofmann, 2011; parental care, Wang et al., 1994; Kleszczyńska et al., 2012; affiliation, Landgraf et al., 2003; Young and Wang, 2004; social approach, Thompson and Walton, 2004; Braida et al., 2012), the AVT/AVP system also regulates central and peripheral…”

“But some researchers have proposed that sex has a secondary function in humans and other animals that require biparental care: It facilitates pair bonding (Birnbaum & Finkel, 2015; Meston & Buss, 2007; Young & Wang, 2004).”

“In voles and rodents, OXT is closely involved in social interactions, social recognition, pair bonding, and maternal behavior (Carter et al., 1992; Winslow and Insel, 2004; Insel and Fernald, 2004; Young and Wang, 2004; Young, 2007; Neumann, 2008; Donaldson and Young, 2008; Insel, 2010; Higashida et al., 2010).”

“Available online at www.sciencedirect.com www.elsevier.com/locate/brainres b r a i n r e s e a r c h 1 5 8 0 ( 2 0 1 4 ) 5 7 – 6 8 0006-8993/$ - see fro http://dx.doi.org/10 nCorresponding a E-mail addresses”

“…voles are small North American rodents that form long-term pairbonds (Getz et al., 1981) – because neurobiological and molecular techniques readily generalize from lab rodents to this less conventional species, the prairie vole has become a major model for social attachment (Young and Wang, 2004).”

“For example, recent work has implicated hormonal modulation of pathways related to reward and reinforcement, as well as those involved in the processing of social information, in elective pair bonding in rodent species such as prairie voles (Young & Wang, 2004).”

“Social learning and memory is only one set of cognitive processes required for partner preference formation in monogamous species (Young & Wang, 2004).”

“OT has been implicated in a suite of prosocial behaviors (MacDonald and MacDonald, 2010), particularly for its facilitative role in social bonding (Young and Wang, 2004).”

“The mesocorticolimbic DA system is well known for its role in regulating motivated behaviors [31].”

“Although nonapeptides are well known for modulating affiliation in monogamous voles (Young and Wang, 2004), surprisingly little is known about the role of these neuropeptides in regulating affiliation in other vertebrates, especially teleosts with monogamous mating systems.”

“For example, the septal nuclei contains neuropeptides such as oxytocin and vasopressin (Loup et al., 1991) that are involved in pair bonding (Young and Wang, 2004).”

“Oxytocinergic afferents in the NAcc are believed to originate from neurons in the hypothalamus (Young & Wang, 2004).”

“The sexually dimorphic nature of the findings in prairie voles may be linked to the neuropeptides associated with pair bonding in male and female voles: AVP and OT, respectively (Young & Wang 2004).”

“For instance, monogamous females show better maternal behavior and more oxytocin receptors in the NAc and prefrontal cortex compared to promiscuous species; while the monogamous males also express better paternal behavior and more vasopressin receptors in the septum and ventral pallidum [93,94].”

“Laboratory data suggest that the avpr1a genotype of male prairie voles has a direct influence on the concentration of V1aRs in their brains and that it is differences in the neural concentration of V1aRs that, in turn, affect male social behaviour (Young & Wang 2004; Hammock & Young 2005).”

“The reason why OT is able to influence multiple processes, such as perception, reward, or pain processing (Young and Wang, 2004; Dölen et al., 2013; Marlin et al., 2015; Eliava et al., 2016; Oettl et al., 2016), is probably because of its modulatory effects on other neurotransmission systems, such as dopamine (Young a…”

“Neuropeptides play a role in regulating a variety of social behaviors (Insel et al., 1998; Young and Wang, 2004); there are significant differences in the distribution of oxytocin and vasopressin receptors between monogamous and polygynous rodent spe- Fig.”

“Notably, both caudate nucleus and ventral pallidum have also been described as critical mediators of rodents’ pair bonding, implicating emotional and social attachment, regulated by oxytocin and the opioid system (Burkett et al., 2011; Young and Wang, 2004).”

“This remarkable species difference in social bonding behavior provides an extraordinarily useful tool for investigating the neurobiological and genetic mechanisms underlying social bond formation (60).”

“Because humans, unlike most mammals, have sex throughout the menstrual cycle rather than just on those days surrounding ovulation, these neuropeptides are secreted in a more distributed manner throughout the cycle and are probably to produce longlasting effects that further reinforce attachment processes [25].”

“…do not demonstrate monogamous mating behavior seem to have similar levels of circulating oxytocin as that of prairie voles, but oxytocin receptor densities vary across species (Buisman-Pijlman et al., 2014), which may contribute to the differences in their mating preferences (Young & Wang, 2004).”

“…including dopamine, oxytocin, and arginine vasopressin, which in turn play important roles in social behaviors such as enduring bonds between mates, selective aggression against novel conspecifics, and enhanced parental care toward offspring (reviewed in Young and Wang, 2004; Young et al., 2011).”

“Based on these and other studies, Young and Wang (2004) proposed that male monogamy in the prairie vole (Microtus ochrogaster) is mediated by an integrated system of neural circuits, which depends critically on the action of AVP on V1aR in the ventral pallidum and lateral septum, and their interactions with regions li…”

“N: 0006-3223 Biolog SEE COMMENTARY vole (Microtus ochrogaster), this rodent species represents a unique animal model to investigate neural circuitry programming pair-bonds (12,13).”

“This analysis did not reveal any significant order effect (for example, for staring duration under saline-OT-AVP conditions, 1-way ANOVA, F(5,264) = 1.”

“While a laundry list of neurotransmitters, peptides, molecules, and genes in the central nervous system (CNS) has been implicated in attachment behaviour in voles (Young & Wang, 2004), here we focus primarily on the role of neuropeptides modulating bonding behaviour and stress.”

“…bonding or pair bonding) (Popik et al., 1992; Benelli et al., 1995; Insel, 1997, 2010; Kendrick, 2000; Young et al., 2001; Wang and Aragona, 2004; Young and Wang, 2004; Ebstein et al., 2009, 2011; Meyer-Lindenberg et al., 2011), and parental care (Modney and Hatton, 1994; Kendrick et al., 1997;…”

“…af fi nity for both D 2 R and OXTR ligands and enhance signaling across OXTR-G a q and D 2 R G a i /o -coupled pathways, while the prosocial and anxiolytic effects of OT can be blocked by a D 2 R antagonist [63,64,68], suggesting that OXTR-D 2 R heterodimer coactivation mediates these effects.”