Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats

Abstract

Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression.

Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats

“…Nucleus accumbens dopamine and social play A Manduca et al that animals isolated for 24 h show a higher motivation for social play behavior in an operant conditioning task than animals isolated for 2 h (Achterberg et al, 2016). As incentive motivation, including motivation for social play (Achterberg et al, 2016), depends on dopaminergic neurotransmission (Kelley, 2004;Barbano and Cador, 2007;Berridge, 2007;Salamone and Correa, 2012), we hypothesized that animals highly motivated for social play behavior as a result of longer social isolation before testing would be more sensitive to blockade of NAc dopamine receptors.…”

“…As incentive motivation, including motivation for social play (Achterberg et al, 2016), depends on dopaminergic neurotransmission (Kelley, 2004;Barbano and Cador, 2007;Berridge, 2007;Salamone and Correa, 2012), we hypothesized that animals highly motivated for social play behavior as a result of longer social isolation before testing would be more sensitive to blockade of NAc dopamine receptors. To test this hypothesis, we investigated the effects of intra-NAc infusion of α-flupenthixol in animals socially isolated for either 24 h or 7 days before testing.…”

“…Social play is highly rewarding, as indicated by operant and place conditioning experiments in rats and primates (Achterberg et al, 2016;Calcagnetti and Schechter, 1992;Falk, 1958;Ikemoto and Panksepp, 1992;Normansell and Panksepp, 1990;. Therefore, it is not surprising that social play is modulated by neurotransmitters involved in reward and motivation (Trezza et al, 2010).…”

“…For example, opioid agonists and drugs that enhance endocannabinoid signaling by interfering with endocannabinoid deactivation increase social play (Trezza et al, 2010). There are several reasons to hypothesize that dopaminergic neurotransmission also has a modulatory role in social play: (1) dopamine plays an important role in certain components of reward processes, such as incentive motivation, incentive salience, and reward prediction (Kelley, 2004;Barbano and Cador, 2007;Berridge, 2007;Salamone and Correa, 2012;Keiflin and Janak, 2015); (2) dopamine utilization increases during social play (Panksepp, 1993); (3) systemic administration of dopamine receptor antagonists reduces social play (Beatty et al, 1984;Niesink and Van Ree, 1989;Siviy et al, 1996;); (4) neonatal 6-hydroxydopamine lesions, which induce profound depletion of striatal dopamine, alter the structure of social play behavior (Pellis et al, 1993); and (5) enhancing dopaminergic activity by blockade of the dopamine transporter increases the motivation for social play (Achterberg et al, 2016). However, contrary to the expectation that drugs that increase dopaminergic neurotransmission would then enhance social play, inconsistent effects have been reported after systemic treatment with dopamine receptor agonists or dopamine reuptake inhibitors (Achterberg et al, 2014;Beatty et al, 1984;Niesink and Van Ree, 1989;Siviy, 1998;Siviy et al, 1996;Vanderschuren et al, 2008).…”

“…Therefore, we separately assessed the contribution of NAc dopamine D1 and D2 receptors in social play behavior. Furthermore, as motivation for social play depends on dopaminergic neurotransmission (Achterberg et al, 2016), we also investigated the role of NAc dopaminergic neurotransmission in social play in animals that differed in their motivation and baseline levels of social play as a result of a longer period of social isolation before testing (Niesink and van Ree, 1989;Vanderschuren et al, 1995aVanderschuren et al, , 2008. Last, as endogenous opioids (Trezza et al, 2011) and endocannabinoids (Trezza et al, 2012) in the NAc mediate social play behavior, and part of the rewarding properties of cannabinoid and opioid drugs involves limbic dopamine-dependent processes (Gardner, 2005;van Ree et al, 1999), we also determined whether NAc dopaminergic neurotransmission underlies the play-enhancing effects mediated by endocannabinoids and opioids.…”