Dopamine regulation of social choice in a monogamous rodent species

“Such behaviors are the result of selection processes that favored reciprocity among close social groups, in which it was adaptive for individuals to spend relatively small amounts of energy to help unrelated members of the group in order to receive relatively large benefi ts of the resulting social organization (Pfeif…”

“…voles show high levels of parental care (Getz and Carter, 1996; Thomas and Birney, 1979) and it has been suggested that both parents are necessary for pup survival which selected for highly enduring pair bonds (Emlen and Oring, 1977; Kleiman, 1977; McGuire et al., 1993; Wang and Novak, 1992).”

“In particular, DA transmission within the NAc is critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice…”

“Finally, we compare these fi ndings to studies that have examined the neural regulation of social decision-making in humans (Fisher et al., 2005; Kosfeld et al., 2005; Rilling et al., 2002).”

“While apomorphine binds both D1 and D2-like receptors, it binds D2-like receptors with a much greater affi nity (Missale et al., 1998).”

“, 2006; Wang and Aragona, 2004; Young and Wang, 2004) and associative learning is signifi cantly regulated by mesolimbic DA transmission (Di Chiara and Bassareo, 2007; Kelley, 2004; Wise, 2004).”

“…because it involves more than one agent and thus requires more sophisticated learning alorithms (Lee, 2008), or if it is more informative to regard social decision-making as largely guided by emotional social motivation and hedonic processing (Sanfey et al., 2003; Skuse and Gallagher, 2009).”

“These data indicate that, under natural circumstances, DA transmission is not uniformly increased as it is under certainly laboratory conditionings (Schultz, 2002).”

“Thus, DA transmission within the NAc shell may regulate partner preference formation through enhanced reward processing or incentive motivation (Berridge, 2007; Di Chiara and Bassareo, 2007).”

“In particular, DA transmission within the NAc is critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice…”

“Here, we describe how the use of one such model system, the socially monogamous prairie vole (Microtus ochrogaster), has signifi cantly advanced our understanding of the neural regulation of social choice behavior (Carter et al., 1995; Dewsbury, 1987; Getz and Carter, 1996; Young and Wang, 2004).”

“This sub-region is critical for processing positive affect and unconditioned aspects of associative learning (Di Chiara and Bassareo, 2007; Ikemoto, 2007; Pecina et al., 2006).”

“Finally, we compare these fi ndings to studies that have examined the neural regulation of social decision-making in humans (Fisher et al., 2005; Kosfeld et al., 2005; Rilling et al., 2002).”

“…voles show high levels of parental care (Getz and Carter, 1996; Thomas and Birney, 1979) and it has been suggested that both parents are necessary for pup survival which selected for highly enduring pair bonds (Emlen and Oring, 1977; Kleiman, 1977; McGuire et al., 1993; Wang and Novak, 1992).”

“Frontiers in Behavioral Neuroscience www.frontiersin.org August 2009 | Volume 3 | Article 15 | 1 BEHAVIORAL NEUROSCIENCE REVIEW ARTICLE published: 11 August 2009 doi: 10.3389/neuro.08.015.2009 and Getz, 1993; Getz and Hofmann, 1986; Insel and Young, 2001).”

“However, it will be necessary for future studies to test this by measuring real-time DA transmission (Aragona et al., 2008; Day et al., 2007; Phillips et al., 2003) during prairie vole social interactions to determine if in vivo DA transmission is consistent with the behavioral pharmacology described in this review.”

“Specifi cally, presentation of a picture of one’s partner increases activation of dopaminergic circuitry in a similar manner as that caused by monetary reward (Aron et al., 2005; Zald et al., 2004).”

“Frontiers in Behavioral Neuroscience www.frontiersin.org August 2009 | Volume 3 | Article 15 | 3 stranger (Williams et al., 1992; Winslow et al., 1993).”

“D1 and D2-like receptors have the opposite effects over cAMP signaling (Neve et al., 2004).”

“In social contexts, decision-making is signifi cantly infl uenced by positive or negative concern for the welfare of others (Fehr and Camerer, 2007).”

“…that this system mediates aspects of reward and emotional processing, its involvement in social decisionmaking among humans may explain why humans often display strong social preferences rather than always acting out of pure selfregard (Camerer and Fehr, 2006; Fehr and Camerer, 2007; Sanfey, 2007).”

“Given that this system mediates aspects of reward and emotional processing, its involvement in social decisionmaking among humans may explain why humans often display strong social preferences rather than always acting out of pure selfregard (Camerer and Fehr, 2006; Fehr and Camerer, 2007; Sanfey, 2007).”

“However, it will be necessary for future studies to test this by measuring real-time DA transmission (Aragona et al., 2008; Day et al., 2007; Phillips et al., 2003) during prairie vole social interactions to determine if in vivo DA transmission is consistent with the behavioral pharmacology described in this review.”

“There are dramatic behavioral alterations as male prairie voles transition from sexually naive to fully pair bonded (Carter et al., 1995).”

“Further, facilitation of partner preference formation by activation of oxytocin receptors is not effective if D2like receptors are blocked (Liu and Wang, 2003).”

“In particular, DA transmission within the NAc is critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice…”

“Pair bond formation is a naturally occurring association formed between monogamous mates (Aragona et al., 2006; Wang and Aragona, 2004; Young and Wang, 2004) and associative learning is signifi cantly regulated by mesolimbic DA transmission (Di Chiara and Bassareo, 2007; Kelley, 2004; Wise, 2004).”

“…(Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007),…”

“However, there has been extensive work conducted on female prairie voles (Cho et al., 1999; Fowler et al., 2002; Insel and Hulihan, 1995; Williams et al., 1992; Witt et al., 1991) and it will be noted when data were collected using female subjects.”

“However, there has been extensive work conducted on female prairie voles (Cho et al., 1999; Fowler et al., 2002; Insel and Hulihan, 1995; Williams et al., 1992; Witt et al., 1991) and it will be noted when data were collected using female subjects.”

“While existing data suggest that pair bond formation is mediated by co-activation of both oxytocin and D2-like DA receptors (Gingrich et al., 2000; Liu and Wang, 2003; Young et al., 2001), it is possible that they represent parallel systems that co-exist within the NAc.”

“This review will focus on data collected from male subjects (Aragona and Wang, 2007; Aragona et al., 2003, 2006).”

“Frontiers in Behavioral Neuroscience www.frontiersin.org August 2009 | Volume 3 | Article 15 | 3 stranger (Williams et al., 1992; Winslow et al., 1993).”

“This species was initially identifi ed as monogamous by fi eld studies which showed that male–female pairs travel together (Getz et al., 1981), share a nest with one or more litters of pups (Getz and Hofmann, 1986), and aggressively repel unrelated intruders from”

“…DA transmission within the NAc is critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice behavior and…”

“This sub-region is critical for processing positive affect and unconditioned aspects of associative learning (Di Chiara and Bassareo, 2007; Ikemoto, 2007; Pecina et al., 2006).”

“Humans display strong social preferences that are revealed through choice behavior in which people behave altruistically, act on a strong sense of fairness, and have tremendous capacities to trust (Krueger et al., 2007; Sanfey, 2007; Tankersley et al., 2007; Zak et al., 2004).”

“REWARD IN PRAIRIE VOLES AND HUMANS Interestingly, the neural regulation of mate choice in humans also involves DA signaling systems (Fisher et al., 2005).”

“We next tested if pharmacological activation of DA receptors within the NAc was suffi cient to induce partner preference formation in the absence of mating (Aragona et al., 2003).”

“…DA transmission within the NAc is critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice behavior and…”

“Indeed, social decision-making in humans is so complex that it can appear to be the result of social cognition that is exclusive to our species (Skuse and Gallagher, 2009).”

“…Robinson et al., 2002), microdialysis measures indicate that mating increases extracellular DA concentration within the NAc of female prairie voles (Gingrich et al., 2000) and tissue extraction studies show that mating also increases dopamine transmission (as indicated by dopamine turnover) in…”

“…cAMP production can be studied by pharmacological blockade of cAMP binding sites on PKA using a cAMP analogue (Rp-cAMPS) whereas increased cAMP production is assessed using a cAMP analogue that binds PKA and releases its regulatory subunits (Sp-cAMPS) (Lynch and Taylor, 2005; Self et al., 1998).”

“Many studies have demonstrated that male prairie voles paired with an estrogen-primed female for 24 h of mating reliably show partner preferences (Aragona et al., 2003; Lim and Young, 2004; Liu et al., 2001) (Figure 1C).”

“Moreover, the fact that a rather large extent of the social organization of prairie voles can be largely explained by rather simple choice behaviors regulated by emotional processing may have very interesting implications for the study of social neuroeconomics (Cacioppo et al., 2000; Lee, 2008).”

“Importantly, the monogamous behaviors observed in nature are also reliably expressed under laboratory conditions (Carter and Getz, 1993; Carter et al., 1995).”

“Such behaviors are the result of selection processes that favored reciprocity among close social groups, in which it was adaptive for individuals to spend relatively small amounts of energy to help unrelated members of the group in order to receive relatively large benefi ts of the resulting social organization (Pfeif…”

“…we have suggested that when pair bonded males in their natural environment encounter a novel female, DA is released in very high concentration (Robinson et al., 2002) suffi cient to activate low affi nity D1-like receptors (Richfi eld et al., 1989), especially since there appear to be a…”

“(A) Cartoon based on (Arbuthnott and Wickens, 2007) showing the portion of the NAc shell where DA manipulations effect pair bond formation.”

“Humans display strong social preferences that are revealed through choice behavior in which people behave altruistically, act on a strong sense of fairness, and have tremendous capacities to trust (Krueger et al., 2007; Sanfey, 2007; Tankersley et al., 2007; Zak et al., 2004).”

“However, if male subjects cohabitate with females for only 6 h without mating, subjects show non- selective side-by-side contact and thus fail to show partner preferences (Aragona and Wang, 2007; Curtis and Wang, 2005; Liu et al., 2001) (Figure 1D).”

“Further, male prairie voles show high levels of parental care (Getz and Carter, 1996; Thomas and Birney, 1979) and it has been suggested that both parents are necessary for pup survival which selected for highly enduring pair bonds (Emlen and Oring, 1977; Kleiman, 1977; McGuire et al.”

“, 1981), share a nest with one or more litters of pups (Getz and Hofmann, 1986), and aggressively repel unrelated intruders from INTRODUCTION In social contexts, decision-making is signifi cantly infl uenced by positive or negative concern for the welfare of others (Fehr and Camerer, 2007).”

“Specifi cally, presentation of a picture of one’s partner increases activation of dopaminergic circuitry in a similar manner as that caused by monetary reward (Aron et al., 2005; Zald et al., 2004).”

“…critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice behavior and decision-making (Phillips et al., 2007).”

“Also consistent with studies conducted in rats (Becker et al., 2001; Pfaus et al., 1995; Robinson et al., 2002), microdialysis measures indicate that mating increases extracellular DA concentration within the NAc of female prairie voles (Gingrich et al., 2000) and tissue extraction studies show…”

“However, it will be necessary for future studies to test this by measuring real-time DA transmission (Aragona et al., 2008; Day et al., 2007; Phillips et al., 2003) during prairie vole social interactions to determine if in vivo DA transmission is consistent with the behavioral pharmacology…”

“A necessary fi rst step in pair bond formation is that males must prefer their familiar partner over new mates, which is very unusual for males in most mammalian species since they reliably prefer to mate with novel females (Fiorino et al., 1997).”

“…2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and Wynne-Edwards, 2006), glutamate and GABA (Curtis and Wang, 2005).”

“Such behaviors are the result of selection processes that favored reciprocity among close social groups, in which it was adaptive for individuals to spend relatively small amounts of energy to help unrelated members of the group in order to receive relatively large benefi ts of the resulting social organization (Pfeif…”

“However, there has been extensive work conducted on female prairie voles (Cho et al., 1999; Fowler et al., 2002; Insel and Hulihan, 1995; Williams et al., 1992; Witt et al., 1991) and it will be noted when data were collected using female subjects.”

“After mating, prairie voles remain together during gestation (McGuire and Novak, 1984; Thomas and Birney, 1979) and this facilitates a successful pregnancy (McGuire et al., 1992).”

“Also consistent with studies conducted in rats (Becker et al., 2001; Pfaus et al., 1995; Robinson et al., 2002), microdialysis measures indicate that mating increases extracellular DA concentration within the NAc of female prairie voles (Gingrich et al., 2000) and tissue extraction studies show…”

“Consistent with data from female prairie voles (Gingrich et al., 2000; Wang et al., 1999), specifi c activation of D2-like receptors within the NAc shell (but not the NAc core) induced partner preferences in the absence of mating (Figure 3A).”

“Humans display strong social preferences that are revealed through choice behavior in which people behave altruistically, act on a strong sense of fairness, and have tremendous capacities to trust (Krueger et al., 2007; Sanfey, 2007; Tankersley et al., 2007; Zak et al., 2004).”

“As in their natural environment, male prairie voles show very high levels of parental care in the lab (Oliveras and Novak, 1986).”

“This supports the view that selection favored organisms that dealt with complex decisions by acting according to the degree of pleasure or displeasure likely to be associated with their behavioral response (Cabanac et al., 2009).”

“As pair bonding involves a myriad of cognitive and psychological processes, it is not surprising that a wide range of neural systems are important for its regulation including: oxytocin (Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et a…”

“For instance, prairie voles preferentially mate with a familiar partner versus a novel conspecifi c (Dewsbury, 1975, 1987; Gray and Dewsbury, 1973).”

“Pair bonded males also choose to aggressively reject potentially new mates (Aragona et al., 2006; Gobrogge et al., 2007).”

“…processes, it is not surprising that a wide range of neural systems are important for its regulation including: oxytocin (Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005;…”

“…2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and Wynne-Edwards, 2006), glutamate and GABA (Curtis and Wang, 2005).”

“…critical for important aspects of reward processing (Berridge and Robinson, 2003; Everitt and Robbins, 2005; Roitman et al., 2005, 2008; Salamone and Correa, 2002; Wheeler et al., 2008) that may underlie cost-benefi t analyses related to choice behavior and decision-making (Phillips et al., 2007).”

“While 24 h of mating increases selective aggression (Wang et al., 1997; Winslow et al., 1993), aggressive behavior is increased much more toward male intruders (compared to novel females) and male subjects do not chase or bite female intruders following 24 h of mating (Wang et al.”

“…Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and…”

“…including: oxytocin (Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995,…”

“…and psychological processes, it is not surprising that a wide range of neural systems are important for its regulation including: oxytocin (Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock…”

“…voles show high levels of parental care (Getz and Carter, 1996; Thomas and Birney, 1979) and it has been suggested that both parents are necessary for pup survival which selected for highly enduring pair bonds (Emlen and Oring, 1977; Kleiman, 1977; McGuire et al., 1993; Wang and Novak, 1992).”

“Pair bond formation is a naturally occurring association formed between monogamous mates (Aragona et al., 2006; Wang and Aragona, 2004; Young and Wang, 2004) and associative learning is signifi cantly regulated by mesolimbic DA transmission (Di Chiara and Bassareo, 2007; Kelley, 2004; Wise, 2004).”

“…voles show high levels of parental care (Getz and Carter, 1996; Thomas and Birney, 1979) and it has been suggested that both parents are necessary for pup survival which selected for highly enduring pair bonds (Emlen and Oring, 1977; Kleiman, 1977; McGuire et al., 1993; Wang and Novak, 1992).”

“If subjects spend signifi cantly more time in side-by-side contact with partners over strangers (assessed by a t-test) then the group is said to show a partner preference (Aragona and Wang, 2004; Curtis and Wang, 2005; Liu et al., 2001).”

“…2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and Wynne-Edwards, 2006), glutamate and GABA (Curtis and Wang, 2005).”

“THE PRAIRIE VOLE MODEL Prairie voles are small rodents (∼40 g) (Figure 1A) distributed primarily in the grasslands of the central United States (Cushing et al., 2001; Hall, 1981; Hoffmann and Koeppl, 1985).”

“, 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and Wynne-Edwards, 2006), glutamate and GABA (Curtis and Wang, 2005).”

“However, there has been extensive work conducted on female prairie voles (Cho et al., 1999; Fowler et al., 2002; Insel and Hulihan, 1995; Williams et al., 1992; Witt et al., 1991) and it will be noted when data were collected using female subjects.”

“Additionally, DA transmission within the NAc shell is also important for mother–offspring bonds, which is an inherently rewarding social attachment (Champagne et al., 2004; Li and Fleming, 2003; Numan et al., 2005).”

“As pair bonding involves a myriad of cognitive and psychological processes, it is not surprising that a wide range of neural systems are important for its regulation including: oxytocin (Bales et al., 2007; Bamshad et al., 1993; Insel and Shapiro, 1992; Liu and Wang, 2003; Witt et al., 1990), vasopressin (Bamshad et a…”

“…2003; Witt et al., 1990), vasopressin (Bamshad et al., 1994; Hammock and Young, 2005; Lim et al., 2004b; Liu et al., 2001; Winslow et al., 1993), corticosterone (DeVries et al., 1995, 1996; Lim et al., 2007), estrogen (Cushing and Wynne-Edwards, 2006), glutamate and GABA (Curtis and Wang, 2005).”

“However, male prairie voles prefer to mate with a familiar female (Dewsbury, 1987) and the presentation of new females does not induce copulation in sexually satiated male prairie voles (Gray and Dewsbury, 1973).”

“Similar to other rodent species (Jansson et al., 1999), prairie vole NAc is densely innervated by dopaminergic terminals arising from the ventral midbrain (Figure 2A) (Aragona et al., 2003; Curtis and Wang, 2005; Gobrogge et al., 2007).”

“After mating, prairie voles remain together during gestation (McGuire and Novak, 1984; Thomas and Birney, 1979) and this facilitates a successful pregnancy (McGuire et al., 1992).”

“…cAMP production can be studied by pharmacological blockade of cAMP binding sites on PKA using a cAMP analogue (Rp-cAMPS) whereas increased cAMP production is assessed using a cAMP analogue that binds PKA and releases its regulatory subunits (Sp-cAMPS) (Lynch and Taylor, 2005; Self et al., 1998).”

“Moreover, the fact that a rather large extent of the social organization of prairie voles can be largely explained by rather simple choice behaviors regulated by emotional processing may have very interesting implications for the study of social neuroeconomics (Cacioppo et al., 2000; Lee, 2008).”

“This review will focus on data collected from male subjects (Aragona and Wang, 2007; Aragona et al., 2003, 2006).”

“Indeed, the pair bond is so stable that a surviving member of the pair will not accept a new mate even if the other member of the bond is lost (Getz and Carter, 1996; Thomas and Wolff, 2004).”

“However, the dynamic interplay between these two peptides and a host of other molecules, such as dopamine (Aragona & Wang 2009, Young et al. 2011) and endogenous opioids (Burkett et al. 2011), supports social behaviors, especially in the face of challenge.”

“to maintain the existing pair bond [8,10] and to limit extra-pair copulations.”

“Pair bonded males will then exhibit affiliative behavior towards their mates while expressing aggressive behavior towards strangers that can be blocked through antagonism of D1-like receptors within the nucleus accumbens (Aragona and Wang, 2009).”

“Many studies have also investigated the role of the mesolimbic dopamine system and opioid regulation of rewarding social behaviors such as pair-bonds between mates (Aragona, 2009; Resendez et al., 2012); we describe these and additional research avenues throughout.”