Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

“Detecting specific V1a and V1b receptors in the brain has been hindered for a long time by the availability of only nonselective radioligands, such as tritium labelled (3H) VP ligands, which bind to both V1 and V2 receptors (Phillips et al., 1990).”

“We discussed above that various rodent species show consistent sex differences in VPimmunoreactive neurons and fiber density in the brain (rats: De Vries et al., 1983; Van Leeuwen et al., 1985; Miller et al., 1989; Wang & De Vries; mice: De Vries et al., 2002; Bakker et al., 2006; Gatewood et al., 2006; Rood & De Vrie…”

“…found higher OTR mRNA expression (Bale and Dorsa, 1995) and higher OTR binding density ([using the specific OTR antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,[125I]Tyr9-NH2]-OVTA; Uhl-Bronner et al., 2005) in males compared to females in the VMH of Long-Evans and Sprague-Dawley rats, respectively.”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“Local VP release in the brain has been measured in male (Veenema et al., 2010; Lukas et al., 2011a) and female (Bosch & Neumann, 2010; Bosch et al., 2010) rats during the expression of social behavior; however, to our knowledge, there are no studies which have compared brain VP release in males and…”

“…of rodent species (summarized in De Vries & Panzica, 2006), including mice (De Vries et al., 2002; Bakker et al., 2006; Gatewood et al., 2006; Rood et al., 2013), voles (Wang, 1995; Wang et al., 1996; Lonstein & De Vries, 1999), gerbils (Crenshaw et al., 1992), European hamsters (but…”

“…as the LS, BNST, nucleus accumbens (NAc), amygdala, diagonal band of Broca, cingulate gyrus, dorsal hippocampus, and caudate nucleus (Baskin et al., 1983; Dorsa et al., 1983; Pearlmutter et al., 1983; Dorsa et al., 1984; Petrecca et al., 1986; Freund-Mercier et al., 1988; Tribollet et al., 1991).”

“No sex differences in OTR binding were found in C57Bl/6J mice (Hammock and Levitt, 2013), the solitary golden hamster (Dubois-Dauphin et al., 1992), prairie voles (Bales et al., 2007a; except for the medial prefrontal cortex in Smeltzer et al., 2006), and humans (Loup et al., 1991).”

“None of these studies found VP-immunoreactive fibers in the LS, while VPimmunoreactive fibers were found in other brain areas (Caffé et al., 1989; Fliers et al., 1986; Wang et al., 1997b).”

“…circulation as a hormone, in which it is involved in maternal responses such as milk ejection and uterine contractions (Fuchs and Poblete, 1970; Belin et al., 1984), in male reproductive functions such as ejaculation, in cardiovascular homeostasis, and other peripheral activities (Gimpl and…”

“However, the underlying mechanisms may be different, because OT decreased sympathetic activity measures during couple conflict in women, but increased sympathetic activity measures in men (Ditzen et al., 2013).”

“These findings were a bit surprising, given the typically pro-social behavior effects of OT, although recent studies suggest a role for the OTR in the LS in reducing pro-social behaviors and enhancing anxiety in rodents (Olazábal and Young, 2006; Beery et al., 2008; Beery and Zucker, 2010; Guzman et al., 2013).”

“injection of an OTR antagonist ([d(CH2)5, Tyr(Me)2, Orn8]Vasotocin) on postnatal day 1 decreased alloparental care in male, but not female, juvenile prairie voles (Bales et al., 2004).”

“In this respect, it is interesting that V1aR binding in the LS positively correlated with maternal aggression in rats (Caughey et al., 2011).”

“…al., 2002; Bakker et al., 2006; Gatewood et al., 2006; Rood et al., 2013), voles (Wang, 1995; Wang et al., 1996; Lonstein & De Vries, 1999), gerbils (Crenshaw et al., 1992), European hamsters (but season-dependent; Buijs et al., 1986), and garden dormice (but season-dependent; Hermes et al., 1990).”

“Interestingly, pregnancy and parturition induce long-lasting enhancements in maternal behaviors during subsequent maternal experiences (Bridges, 1975, 1977; Nephew et al., 2009; Macbeth & Luine, 2010).”

“Studies in non-human primates have also reported an absence of sex differences in OT-immunoreactive neurons in macaques (PVN, SON: Caffé et al., 1989) and marmosets (PVN, SON, BNST, MeA: Wang et al., 1997).”

“Indeed, later studies consistently found higher OTR mRNA expression (Bale and Dorsa, 1995) and higher OTR binding density ([using the specific OTR antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,[125I]Tyr9-NH2]-OVTA; Uhl-Bronner et al., 2005) in males compared to females in the VMH of Long-Evans and…”

“The V1bR has been more recently getting recognized as a modulator of various social behaviors, such as social recognition, aggression, and maternal care (Stevenson & Caldwell, 2012).”

“For example, female mandarin voles (Cao et al., 2013) prairie voles (Kramer et al., 2004) and Sprague Dawley rats (Kramer et al., 2004) had higher plasma OT concentrations compared to males, yet only female mandarin voles had higher OT-immunoreactivity in the PVN and SON (Qiao et al., 2014).”

“…anestrus female Syrian hamsters have lower V1aR binding in the medial preoptic nucleus, MPOA, LH, CeA, and BNST compared to females on a long photoperiod (Caldwell and Albers, 2004b), suggesting gonadal hormonal control of V1aR in various brain regions of both male and female hamsters.”

“Re-expression of V1aR in the LS of V1aR KO mice restored social recognition (Bielsky et al., 2005a), thereby confirming studies in rats showing the importance of the LS-VP system in social recognition.”

“(Armstrong, 2004).”

“There is also a lack of sex differences in OT neuron size and number in humans (Fliers et al., 1985; Wierda et al., 1991; Ishunina and Swaab, 1999), and most human studies report a lack of sex differences in plasma OT (Zhong et al., 2012; Taylor et al., 2010; Grewen et al., 2005; Gordon et al.,…”

“, 2013), voles (Wang, 1995; Wang et al., 1996; Lonstein & De Vries, 1999), gerbils (Crenshaw et al.”

“, 1991; Ishunina and Swaab, 1999), and most human studies report a lack of sex differences in plasma OT (Zhong et al., 2012; Taylor et al., 2010; Grewen et al., 2005; Gordon et al., 2008; Gordon et al., 2010; Graugaard-Jensen et al., 2014; however see van Londen et al., 1997; Miller et al., 2013; Weisman et al., 2013).”

“VP and OT systems have been implicated in sex-biased psychiatric disorders of social dysfunction, such as autism spectrum disorder and schizophrenia(Green et al., 2001; Wu et al., 2005; Jacob et al., 2007; Campbell et al., 2011; Miller et al., 2013; Di Napoli et al., 2014; Golimbet et al., 2014; Jobst et al., 2014).”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Young et al., 2000).”

“In rodents, sex-specific regulation of partner preference in prairie voles, social recognition in rats, social play in rats, and aggression in hamsters has been found (Dantzer et al., 1987; Bluthe & Dantzer, 1990; Winslow et al., 1993; Insel & Hulihan, 1995; Ferris et al., 1997; Cho et al., 1999; Caldwell and Albers,…”

“…gene expression through binding to the estrogen receptor alpha, which is a transcription factor that modulates gene transcription via interaction with estrogen response elements located on the promotor region of the OTR gene (Carson-Jurica et al., 1990; Young et al., 1998; Ivell & Walther, 1999).”

“…in the PVN of adult Wistar rats (Table 4), higher VP mRNA expression in the SON was found in juvenile male compared to juvenile female Wistar rats (Taylor et al., 2012) and larger VP neurons in the SON were found in adult male compared to adult female Sprague-Dawley rats (Madeira et al., 1993).”

“Schmidt et al. (1991) further developed a linear antagonist specific to the V1aR.”

“Although the V2R has been reported to be found in the rat brain (Hirasawa et al., 1994; Kato et al., 1995), this has not recently been confirmed, and evidence of the presence of V2R in the brain is largely lacking.”

“Here, impaired social recognition was found in male OTR KO mice (Takayanagi et al., 2005; Lee et al., 2008; Macbeth et al., 2009), male OT KO mice (Ferguson et al., 2000; Macbeth et al., 2009), and female OT KO mice (Choleris et al., 2003; Choleris et al, 2006).”

“…rats were used, this was the first study to show V1R-specific binding in the hypothalamus, NAc, LS, BNST, central amygdala (CeA), nucleus of the solitary tract, islands of Calleja, lateral olfactory tract, choroid plexi, and stigmoid hypothalamic nucleus (StigH; Gerstberger & Fahrenholz, 1989).”

“…OT synthesizing cells are found in the accessory magnocellular nucleus of the hypothalamus (rats, humans: Fliers et al., 1985; Weirda et al., 1991; Meynen et al., 2007) or LH, AH, and MPOA (hamsters, gerbils, voles, naked mole rats: Brownstein et al., 1980; Dierickx, 1980; Rhodes et al., 1981;…”

“In addition, VP-synthesizing cells in the PVN, SON, suprachiasmatic nucleus of the hypothalamus (SCN), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA) project centrally to multiple areas in the brain (Buijs, 1978; Sofroniew and Weindl, 1978; Buijs and Swaab, 1979; Buijs, 1980; Sofroniew, 1980; Sof…”

“…Fliers et al., 1985; Weirda et al., 1991; Meynen et al., 2007) or LH, AH, and MPOA (hamsters, gerbils, voles, naked mole rats: Brownstein et al., 1980; Dierickx, 1980; Rhodes et al., 1981; Swanson and Sawchenko, 1983; Wang et al., 1996; Rosen et al., 2008; Xu et al., 2010; Wang et al., 2013).”

“…been carried out in men and have revealed a facilitating role of VP in the encoding of happy and angry faces (Guastella et al., 2010b; however, see Uzefovsky et al., 2012), the recognition of sexual cues (Guastella et al., 2011), the perception of neutral facial expressions as being angry…”

“Although the V2R has been reported to be found in the rat brain (Hirasawa et al., 1994; Kato et al., 1995), this has not recently been confirmed, and evidence of the presence of V2R in the brain is largely lacking.”

“Specifically, while there was no effect in females, males with the DupB−/− allele (which is the shorter bp version and lacks RS3) needed more social cues to elicit an orienting response than males with the DupB+/− (which have one copy of the long allele containing RS3; Hopkins et al., 2014).”

“…spinal fluid compared to men irrespective of health condition (i.e., in healthy controls and in patients with obsessive compulsive disorder; Altemus et al., 1999), suggesting that brain OT release may be higher in females, regardless of the lack of sex differences in OT synthesis in the…”

“, 2007), as well as in animal models of social dysfunction (Dieckmann et al., 2007; Koh et al., 2008).”

“Using the same 125I linear V1aR antagonist, additional V1aR binding sites were found in the frontal cortex, dorsal hypothalamus, AH, hippocampal dentate gyrus (DG), substantia nigra, and ventral tegmental area (VTA; Johnson et al., 1993)of male rats.”

“…release, because investigation into brain region-specific OT release patterns in rats have been performed in one sex only (males: Engelmann et al., 1999; Ebner et al., 2000; Waldherr and Neumann, 2007; or females: Nyuyki et al., 2011; Neumann et al., 1993; Bosch et al., 2010; Bosch et al., 2004).”

“Studies in non-human primates have also reported an absence of sex differences in OT-immunoreactive neurons in macaques (PVN, SON: Caffé et al., 1989) and marmosets (PVN, SON, BNST, MeA: Wang et al., 1997).”

“In addition, intranasal VP altered social recognition-processing regions, such as the temporoparietal junction, caused by social unfamiliarity (Zink et al., 2011), and activation in the right superior temporal sulcus during reactive aggression (Brunnlieb et al., 2013a) in men.”

“In detail, VP synthesis in hypothalamic regions is similar between male and female mice (PVN and SON: Joca et al., 2013; Steinman et al., 2015), voles (PVN, SON, SCN in prairie, pine, meadow, and montane voles: Wang, 1995; Wang et al., 1996), Mongolian gerbils (PVN, medial preoptic area [MPOA],…”

“Specifically, while there was no effect in females, males with the DupB−/− allele (which is the shorter bp version and lacks RS3) needed more social cues to elicit an orienting response than males with the DupB+/− (which have one copy of the long allele containing RS3; Hopkins et al., 2014).”

“…as the LS, BNST, nucleus accumbens (NAc), amygdala, diagonal band of Broca, cingulate gyrus, dorsal hippocampus, and caudate nucleus (Baskin et al., 1983; Dorsa et al., 1983; Pearlmutter et al., 1983; Dorsa et al., 1984; Petrecca et al., 1986; Freund-Mercier et al., 1988; Tribollet et al., 1991).”

“Moreover, neonatal OT increased ERα-immunoreactivity in the VMH while OTR antagonist decreased ERαimmunoreactivity in the MPOA in females, but not males (Yamamoto et al., 2006).”

“For example, V1aR has been implicated in pair bonding, maternal care, aggression, social recognition, and social play (Bielsky et al., 2004; Egashira et al., 2004; Lim et al., 2004b; Bosch and Neumann, 2008; Veenema and Neumann, 2008; Veenema et al., 2013; Albers, 2014).”

“, 2014), while AVP1A gene variants had sex-specific effects on pair-bondng and prepulse inhibition (Walum et al., 2008; Levin et al., 2009).”

“On the other hand, a recent study which did include both men and women found that VP influenced empathic concern in men and women with no effect of sex (Tabak et al., 2015).”

“…as the LS, BNST, nucleus accumbens (NAc), amygdala, diagonal band of Broca, cingulate gyrus, dorsal hippocampus, and caudate nucleus (Baskin et al., 1983; Dorsa et al., 1983; Pearlmutter et al., 1983; Dorsa et al., 1984; Petrecca et al., 1986; Freund-Mercier et al., 1988; Tribollet et al., 1991).”

“…in several hypothalamic areas (namely the ventrolateral hypothalamus, ventromedial MPOA, lateral MPOA, posterior lateral preoptic area, anterior LH, and ventromedial hypothalamus[VMH]) of male hamsters (Delville & Ferris, 1995; Johnson et al., 1995; Dumais and Veenema Page 10 Front Neuroendocrinol.”

“Girls who experienced stressful life events and were CT- and TTcarriers had increased numbers of emotional problems, while boys who experienced stressful events and were TT-homozygotes had an increase in peer problems (Loth et al., 2014).”

“Interestingly, pregnancy and parturition induce long-lasting enhancements in maternal behaviors during subsequent maternal experiences (Bridges, 1975, 1977; Nephew et al., 2009; Macbeth & Luine, 2010).”

“For example, in men, intranasal VP altered activation and connectivity in a medial prefrontal cortex-amygdala circuit during processing of facial emotions (Zink et al., 2010) and when viewing pictures illustrating socially threatening scenes (Brunnlieb et al., 2013b).”

“Additional studies implicated a role of the VP system in the LS and olfactory bulb in the regulation of social recognition (Le Moal et al., 1987; Dantzer, 1998; Engelmann & Landgraf, 1994; Everts & Koolhaas, 1999; Landgraf et al., 2003; Tobin et al., 2010), but these studies were conducted in males…”

“, 2013), adult men (Share et al., 1988; Van Londen et al., 1997) but also in elderly men (Asplund & Aberg, 1991).”

“, 2014), autism (Yang et al., 2010; Xu et al., 2013; LoParo and Waldman, 2014), depression (Yuen et al.”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“, 2012), the recognition of sexual cues (Guastella et al., 2011), the perception of neutral facial expressions as being angry (Thompson et al.”

“…al., 2002; Bakker et al., 2006; Gatewood et al., 2006; Rood et al., 2013), voles (Wang, 1995; Wang et al., 1996; Lonstein & De Vries, 1999), gerbils (Crenshaw et al., 1992), European hamsters (but season-dependent; Buijs et al., 1986), and garden dormice (but season-dependent; Hermes et al., 1990).”

“…have been implicated in sex-biased psychiatric disorders of social dysfunction, such as autism spectrum disorder and schizophrenia(Green et al., 2001; Wu et al., 2005; Jacob et al., 2007; Campbell et al., 2011; Miller et al., 2013; Di Napoli et al., 2014; Golimbet et al., 2014; Jobst et al., 2014).”

“Using the 125I linear V1aR antagonist, it was found that female C57B6 mice (n=5) had higher V1aR binding in the MPOA and mammillary nuclei compared to males (n=5; Dubois Dauphin et al., 1996).”

“Given the role of VP in modulating maternal behavior in rodents (Bosch & Neumann, 2008; Nephew & Bridges, 2008), it is likely that such changes in V1aR may mediate optimal maternal care.”

“Likewise, women only were tested for social auditory processing and those carrying the A allele reported more difficulty hearing and understanding people when there was background noise present (Tops et al., 2011).”

“In contrast to the BNST and MeA, no sex differences in VP mRNA expression in the PVN have been found in adult rats (Table 4), nor in weanling (Paul et al., 2014) or juvenile (Taylor et al., 2014) rats.”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“…in the PVN of adult Wistar rats (Table 4), higher VP mRNA expression in the SON was found in juvenile male compared to juvenile female Wistar rats (Taylor et al., 2012) and larger VP neurons in the SON were found in adult male compared to adult female Sprague-Dawley rats (Madeira et al., 1993).”

“, 1986), and garden dormice (but season-dependent; Hermes et al., 1990).”

“Siberian hamsters (V1R) VMH, medial tuberal-, ventral premammilaryhypothalamus Dubois-Dauphin et al. (1991)”

“…as the LS, BNST, nucleus accumbens (NAc), amygdala, diagonal band of Broca, cingulate gyrus, dorsal hippocampus, and caudate nucleus (Baskin et al., 1983; Dorsa et al., 1983; Pearlmutter et al., 1983; Dorsa et al., 1984; Petrecca et al., 1986; Freund-Mercier et al., 1988; Tribollet et al., 1991).”

“, 2014), autism (Yang et al., 2010; Xu et al., 2013; LoParo and Waldman, 2014), depression (Yuen et al.”

“(Lynn et al., 2014), and slowed reaction times in an implicit perspective taking task in men to that of the level of women (Theodoridou et al.”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“Overall, these findings clearly indicate that, similar to OT-immunoreactivity, there are robust brain region- and species-specific sex differences in OTR expression in the brain.”

“, 2014), and slowed reaction times in an implicit perspective taking task in men to that of the level of women (Theodoridou et al., 2013).”

“Intranasal OT impaired recognition memory of neutral and happy faces in men, but not women (Herzmann et al., 2013), and facilitated kinship recognition in women, but not men (Fischer-Shofty et al., 2013).”

“Also, male golden hamsters showed more VP-immunoreactive neurons in the SON, but not the PVN, compared to female golden hamsters (Delville et al., 1994).”

“…as the LS, BNST, nucleus accumbens (NAc), amygdala, diagonal band of Broca, cingulate gyrus, dorsal hippocampus, and caudate nucleus (Baskin et al., 1983; Dorsa et al., 1983; Pearlmutter et al., 1983; Dorsa et al., 1984; Petrecca et al., 1986; Freund-Mercier et al., 1988; Tribollet et al., 1991).”

“For example, in men, intranasal VP altered activation and connectivity in a medial prefrontal cortex-amygdala circuit during processing of facial emotions (Zink et al., 2010) and when viewing pictures illustrating socially threatening scenes (Brunnlieb et al., 2013b).”

“This effect was also found in male, but not female, adult ICR mice (Mogi et al., 2014), although neonatal OTR blockade reduced social approach behavior in female, but not male, ICR mice (Mogi et al., 2014).”

“No sex differences in OTR binding were found in C57Bl/6J mice (Hammock and Levitt, 2013), the solitary golden hamster (Dubois-Dauphin et al., 1992), prairie voles (Bales et al.”

“Studies in non-human primates have also reported an absence of sex differences in OT-immunoreactive neurons in macaques (PVN, SON: Caffé et al., 1989) and marmosets (PVN, SON, BNST, MeA: Wang et al., 1997).”

“…for OT mRNA expression in Wistar rats (PVN, SON: Dumais et al., 2013) or for OTimmunoreactive neurons in prairie, pine, meadow, and montane voles (PVN, SON, MPOA, BNST: Wang et al., 1996), naked mole rats (PVN, SON: Rosen et al., 2008), and long tailed hamsters (PVN, MPOA, LH, AH: Xu et al., 2010).”

“…in VP neurons and plasma VP concentrations have also been found in humans (Share et al., 1988; Asplund & Aberg, 1991; Van Londen et al., 1997; Ishinina et al., 1999; Miller et al., 2013; Graugaard-Jensen et al., 2014; however, see Fliers et al., 1985; Swaab et al., 2001; Gouin et al., 2012).”

“Overall, these findings clearly indicate that, similar to OT-immunoreactivity, there are robust brain region- and species-specific sex differences in OTR expression in the brain.”

“…per sex, which might explain the limited brain regions in which sex differences in V1aR binding were found (C57B6 mice: Dubois Dauphin et al., 1996; Siberian hamsters: Dubois-Dauphlin et al., 1991; golden hamsters: Delville & Ferris, 1995; voles: Bales et al., 2007a; Smeltzer et al., 2006).”

“, 2007), as well as in animal models of social dysfunction (Dieckmann et al., 2007; Koh et al., 2008).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript it is involved in the regulation of blood pressure and water retention in the body (Silva et al., 1969; Ishikawa, 1993).”

“…anestrus female Syrian hamsters have lower V1aR binding in the medial preoptic nucleus, MPOA, LH, CeA, and BNST compared to females on a long photoperiod (Caldwell and Albers, 2004b), suggesting gonadal hormonal control of V1aR in various brain regions of both male and female hamsters.”

“Likewise, although no sex differences were found in the hippocampal CA1 region, SSc, LS, and VTA of C57B6 mice (Hammock and Levitt, 2012), other brain regions were not tested for sex differences and the number of mice per sex (n”

“…V1aR antagonist has been developed for the use in PET and SPECT imaging, which may lead to a further understanding of sex differences in the brain V1aR system in humans, including the potential relation of V1aR binding with brain function and vasopressin-related disorders (Fabio et al., 2012).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript it is involved in the regulation of blood pressure and water retention in the body (Silva et al., 1969; Ishikawa, 1993).”

“VP and OT systems have been implicated in sex-biased psychiatric disorders of social dysfunction, such as autism spectrum disorder and schizophrenia(Green et al., 2001; Wu et al., 2005; Jacob et al., 2007; Campbell et al., 2011; Miller et al., 2013; Di Napoli et al., 2014; Golimbet et al., 2014; Jobst et al., 2014).”

“…in VP neurons and plasma VP concentrations have also been found in humans (Share et al., 1988; Asplund & Aberg, 1991; Van Londen et al., 1997; Ishinina et al., 1999; Miller et al., 2013; Graugaard-Jensen et al., 2014; however, see Fliers et al., 1985; Swaab et al., 2001; Gouin et al., 2012).”

“In ICR mice, using the 125I linear V1aR antagonist, males (n=6) and females (n=6) showed a lack of sex differences in all regions analyzed (subfornical organ, LS, PVN, paraventricular thalamus, mammillary complex, parabrachial nucleus, area postrema-nucleus of the solitary tract, and hypoglossal nucleus; Tribollet et…”

“Taken together, across vertebrate species, VP synthesis and projections in the brain are often sexually dimorphic, VP within the BNST/MeA is modulated by gonadal hormones, and sex differences in VP may be sensitive to changes in status (dominant, subordinate), season, and photoperiod.”

“Furthermore, testosterone treatment increased vasotocin V1aR binding in nuclei of the song system in female canaries (Voorhuis et al., 1988) and male white-throated sparrows (Grozhik et al., 2014).”

“This may be one of the mechanisms by which neonatal OT and OTR antagonist have long-lasting sex-specific effects on social behaviors and brain parameters (Bales and Carter, 2003a,b; Carter et al., 2008; Mogi et al., 2014).”

“, 2004), and in musical working memory (Granot et al., 2013).”

“Expression of this potent neuromodulator has been found in brain regions including the BST, medial amygdala (MeA), supraoptic nucleus (SON), suprachiasmatic nucleus, and PVN (Dumais & Veenema, 2016; Whitnall, Mezey, & Gainer, 1985).”

“These steps were not taken here because although V1a receptor mRNA has been reported throughout cortex 60 V1a receptor binding is not evident in adult male rat insula 61 .”