Abstract
Social play behavior is a highly rewarding form of social interaction displayed by young mammals. Social play is important for neurobehavioral development and it has been found to be impaired in several developmental psychiatric disorders. In line with the rewarding properties of social play, we have previously identified the nucleus accumbens (NAc) as an important site of action for endocannabinoid and opioid modulation of this behavior. NAc dopamine has a well-known role in certain components of reward processes, such as incentive motivation. However, its contribution to the positive emotional aspects of social interactions is less clear. Therefore, we investigated the role of dopaminergic neurotransmission in the NAc in social play behavior in rats. We found that intra-NAc infusion of the dopamine releaser/reuptake inhibitor amphetamine increased social play behavior that was dependent on activation of both D1 and D2 dopamine receptors. This increase in social play behavior was mimicked by intra-NAc infusion of the dopamine receptor agonist apomorphine, but not of the dopamine reuptake inhibitor GBR-12909. Blockade of either D1 or D2 NAc dopamine receptors reduced social play in animals highly motivated to play as a result of longer social isolation before testing. Last, blockade of NAc dopamine receptors prevented the play-enhancing effects of endocannabinoid and opioid receptor stimulation. These findings demonstrate an important modulatory role of NAc dopaminergic neurotransmission in social play. Thus, functional activity in the mesolimbic dopamine pathway plays an important role in adaptive social development, whereas abnormal NAc dopamine function may underlie the social impairments observed in developmental psychiatric disorders such as autism, attention deficit hyperactivity disorder or early-onset schizophrenia.
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References
Achterberg EJM, Trezza V, Siviy SM, Schrama L, Schoffelmeer ANM, Vanderschuren LJMJ (2014). Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms. Psychopharmacology 231: 1503–1515.
Achterberg EJM, van Kerkhof LW, Damsteegt R, Trezza V, Vanderschuren LJMJ (2015). Methylphenidate and atomoxetine inhibit social play behavior through prefrontal and subcortical limbic mechanisms in rats. J Neurosci 35: 161–169.
Achterberg EJM, van Kerkhof LW, Servadio M, van Swieten MM, Houwing DJ, Aalderink M et al (2016). Contrasting roles of dopamine and noradrenaline in the motivational properties of social play behavior in rats. Neuropsychopharmacology 41: 858–868.
Alessandri SM (1992). Attention, play, and social behavior in ADHD preschoolers. J Abnorm Child Psychol 20: 289–302.
Barbano MF, Cador M (2007). Opioids for hedonic experience and dopamine to get ready for it. Psychopharmacology (Berl) 191: 497–506.
Beatty WW, Costello KB, Berry SL (1984). Suppression of play fighting by amphetamine: effects of catecholamine antagonists, agonists and synthesis inhibitors. Pharmacol Biochem Behav 20: 747–755.
Berridge KC (2007). The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology (Berl) 191: 391–431.
Berridge KC, Kringelbach ML (2008). Affective neuroscience of pleasure: reward in humans and animals. Psychopharmacology (Berl) 199: 457–480.
Bowton E, Saunders C, Reddy IA, Campbell NG, Hamilton PJ, Henry LK et al (2014). SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking. Transl Psychiatry 4: e464.
Calcagnetti DJ, Schechter MD (1992). Place conditioning reveals the rewarding aspect of social interaction in juvenile rats. Physiol Behav 51: 667–672.
Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002). Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26: 321–352.
Daberkow DP, Brown HD, Bunner KD, Kraniotis SA, Doellman MA, Ragozzino ME et al (2013). Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. J Neurosci 33: 452–463.
Eisenegger C, Pedroni A, Rieskamp J, Zehnder C, Ebstein R, Fehr E et al (2013). DAT1 polymorphism determines L-DOPA effects on learning about others' prosociality. PLoS One 8: e67820.
Enter D, Colzato LS, Roelofs K (2012). Dopamine transporter polymorphisms affect social approach-avoidance tendencies. Genes Brain Behav 11: 671–676.
Everitt BJ, Robbins TW (2005). Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8: 1481–1489.
Falk JL (1958). The grooming behavior of the chimpanzee as a reinforcer. J Exp Anal Behav 1: 83–85.
Fernández-Ruiz J, Hernández M, Ramos JA (2010). Cannabinoid-dopamine interaction in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther 16: e72–e91.
Floresco SB (2015). The nucleus accumbens: an interface between cognition, emotion, and action. Annu Rev Psychol 66: 25–52.
Gardner EL (2005). Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81: 263–284.
Gerfen CR, Surmeier DJ (2011). Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34: 441–466.
Gordon NS, Kollack-Walker S, Akil H, Panksepp J (2002). Expression of c-fos gene activation during rough and tumble play in juvenile rats. Brain Res Bull 57: 651–659.
Gunaydin LA, Deisseroth K (2014). Dopaminergic dynamics contributing to social behavior. Cold Spring Harb Symp Quant Biol 79: 221–227.
Hettinger JA, Liu X, Schwartz CE, Michaelis RC, Holden JJ (2008). A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families. Am J Med Genet B Neuropsychiatr Genet 147B: 628–636.
Hol T, Van den Berg CL, Van Ree JM, Spruijt BM (1999). Isolation during the play period in infancy decreases adult social interactions in rats. Behav Brain Res 100: 91–97.
Ikemoto S, Panksepp J (1992). The effects of early social isolation on the motivation for social play in juvenile rats. Dev Psychobiol 25: 261–274.
Jalabert M, Bourdy R, Courtin J, Veinante P, Manzoni OJ, Barrot M et al (2011). Neuronal circuits underlying acute morphine action on dopamine neurons. Proc Natl Acad Sci USA 108: 16446–16450.
Johnson SW, North RA (1992). Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12: 483–488.
Jordan R (2003). Social play and autistic spectrum disorders: a perspective on theory, implications and educational approaches. Autism 7: 347–360.
Keiflin R, Janak PH (2015). Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry. Neuron 88: 247–263.
Kelley AE (2004). Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 27: 765–776.
Kravitz AV, Tye LD, Kreitzer AC (2012). Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat Neurosci 15: 816–818.
Loureiro M, Renard J, Zunder J, Laviolette SR (2015). Hippocampal cannabinoid transmission modulates dopamine neuron activity: impact on rewarding memory formation and social interaction. Neuropsychopharmacology 40: 1436–1447.
Niesink RJ, Van Ree JM (1989). Involvement of opioid and dopaminergic systems in isolation-induced pinning and social grooming of young rats. Neuropharmacology 28: 411–418.
Normansell L, Panksepp J (1990). Effects of morphine and naloxone on play-rewarded spatial discrimination in juvenile rats. Dev Psychobiol 23: 75–83.
Panksepp J (1993). Rough and tumble play: a fundamental brain process. In: MacDonald K (ed). Parent–Child Play. SUNY Press: Albany, pp 147–184.
Panksepp J, Siviy S, Normansell L (1984). The psychobiology of play: theoretical and methodological perspectives. Neurosci Biobehav Rev 8: 465–492.
Pellis S, Pellis V (2009) The Playful Brain: Venturing to the Limits of Neuroscience. Oneworld Publications: Oxford, UK.
Pellis SM, Castaneda E, McKenna MM, Tran-Nguyen LT, Whishaw IQ (1993). The role of the striatum in organizing sequences of play fighting in neonatally dopamine-depleted rats. Neurosci Lett 158: 13–15.
Pierce RC, Kumaresan V (2006). The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30: 215–238.
Robinson DL, Heien ML, Wightman RM (2002). Frequency of dopamine concentration transients increases in dorsal and ventral striatum of male rats during introduction of conspecifics. J Neurosci 22: 10477–10486.
Robinson DL, Zitzman DL, Smith KJ, Spear LP (2011). Fast dopamine release events in the nucleus accumbens of early adolescent rats. Neuroscience 176: 296–307.
Rodriguez-Arias M, Pinazo J, Minarro J, Stinus L (1999). Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice. Pharmacol Biochem Behav 64: 123–130.
Salamone JD, Correa M (2012). The mysterious motivational functions of mesolimbic dopamine. Neuron 76: 470–485.
Siviy SM (1998). Neurobiological substrates of play behavior: glimpses into the structure and function of mammalian playfulness. In: Bekoff M, Byers JA (eds). Animal Play: Evolutionary, Comparative, and Ecological Perspectives. Cambridge University Press: Cambridge, pp 221–242.
Siviy SM, Crawford CA, Akopian G, Walsh JP (2011). Dysfunctional play and dopamine physiology in the Fischer 344 rat. Behav Brain Res 220: 294–304.
Siviy SM, Fleischhauer AE, Kerrigan LA, Kuhlman SJ (1996). D2 dopamine receptor involvement in the rough-and-tumble play behavior of juvenile rats. Behav Neurosci 110: 1168–1176.
Trezza V, Baarendse PJ, Vanderschuren LJMJ (2010). The pleasures of play: pharmacological insights into social reward mechanisms. Trends Pharmacol Sci 31: 463–469.
Trezza V, Damsteegt R, Achterberg EJM, Vanderschuren LJMJ (2011). Nucleus accumbens mu-opioid receptors mediate social reward. J Neurosci 31: 6362–6370.
Trezza V, Damsteegt R, Manduca A, Petrosino S, Van Kerkhof LW, Pasterkamp RJ et al (2012). Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats. J Neurosci 32: 14899–14908.
Trezza V, Damsteegt R, Vanderschuren LJMJ (2009). Conditioned place preference induced by social play behavior: parametrics, extinction, reinstatement and disruption by methylphenidate. Eur Neuropsychopharmacol 19: 659–669.
Trezza V, Vanderschuren LJMJ (2008). Bidirectional cannabinoid modulation of social behavior in adolescent rats. Psychopharmacology (Berl) 197: 217–227.
Trezza V, Vanderschuren LJMJ (2009). Divergent effects of anandamide transporter inhibitors with different target selectivity on social play behavior in adolescent rats. J Pharmacol Exp Ther 328: 343–350.
van Furth WR, Wolterink G, van Ree JM (1995). Regulation of masculine sexual behavior: involvement of brain opioids and dopamine. Brain Res Brain Res Rev 21: 162–184.
van Kerkhof LW, Damsteegt R, Trezza V, Voorn P, Vanderschuren LJMJ (2013). Social play behavior in adolescent rats is mediated by functional activity in medial prefrontal cortex and striatum. Neuropsychopharmacology 38: 1899–1909.
van Kerkhof LW, Trezza V, Mulder T, Gao P, Voorn P, Vanderschuren LJMJ (2014). Cellular activation in limbic brain systems during social play behaviour in rats. Brain Struct Funct 219: 1181–1211.
van Ree JM, Gerrits MA, Vanderschuren LJMJ (1999). Opioids, reward and addiction: an encounter of biology, psychology, and medicine. Pharmacol Rev 51: 341–396.
Vanderschuren LJMJ, Niesink RJ, Spruijt BM, Van Ree JM (1995a). Effects of morphine on different aspects of social play in juvenile rats. Psychopharmacology (Berl) 117: 225–231.
Vanderschuren LJMJ, Stein EA, Wiegant VM, Van Ree JM (1995b). Social play alters regional brain opioid receptor binding in juvenile rats. Brain Res 680: 148–156.
Vanderschuren LJMJ, Trezza V, Griffioen-Roose S, Schiepers OJ, Van Leeuwen N, De Vries TJ et al (2008). Methylphenidate disrupts social play behavior in adolescent rats. Neuropsychopharmacology 33: 2946–2956.
Volkow ND, Morales M (2015). The brain on drugs: from reward to addiction. Cell 162: 712–725.
Voorn P, Vanderschuren LJMJ, Groenewegen HJ, Robbins TW, Pennartz CMA (2004). Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci 27: 468–474.
Whitaker LR, Degoulet M, Morikawa H (2013). Social deprivation enhances VTA synaptic plasticity and drug-induced contextual learning. Neuron 77: 335–345.
Yorgason JT, Calipari ES, Ferris MJ, Karkhanis AN, Fordahl SC, Weiner JL et al (2016). Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum. Neuropharmacology 101: 471–479.
Yorgason JT, España RA, Konstantopoulos JK, Weiner JL, Jones SR (2013). Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci 37: 1022–1031.
Young LJ, Wang Z (2004). The neurobiology of pair bonding. Nat Neurosci 7: 1048–1054.
Acknowledgements
This study was supported by the Netherlands Organization for Scientific Research (NWO) Veni grant 91611052 (to VT), Marie Curie Career Reintegration grant PCIG09-GA-2011-293589 (to VT), and the National Institute on Drug Abuse grant R01 DA022628 (to LJMJV), The Netherlands.
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Manduca, A., Servadio, M., Damsteegt, R. et al. Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats. Neuropsychopharmacol 41, 2215–2223 (2016). https://doi.org/10.1038/npp.2016.22
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DOI: https://doi.org/10.1038/npp.2016.22
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