The neurobiology of social play and its rewarding value in rats

Abstract

In the young of many mammalian species, including humans, a vigorous and highly rewarding social activity is abundantly expressed, known as social play behaviour. Social play is thought to be important for the development of social, cognitive and emotional processes and their neural underpinnings, and it is disrupted in pediatric psychiatric disorders. Here, we summarize recent progress in our understanding of the brain mechanisms of social play behaviour, with a focus on its rewarding properties. Opioid, endocannabinoid, dopamine and noradrenaline systems play a prominent role in the modulation of social play. Of these, dopamine is particularly important for the motivational properties of social play. The nucleus accumbens has been identified as a key site for opioid and dopamine modulation of social play. Endocannabinoid influences on social play rely on the basolateral amygdala, whereas noradrenaline modulates social play through the basolateral amygdala, habenula and prefrontal cortex. In sum, social play behaviour is the result of coordinated activity in a network of corticolimbic structures, and its monoamine, opioid and endocannabinoid innervation.

Keywords: Amygdala; Dopamine; Endocannabinoids; Noradrenaline; Nucleus accumbens; Operant conditioning; Opioids; Place conditioning; Prefrontal cortex; Reward; Social play behaviour.

Figure 1. Correlations of social play parameters with conditioned place preference

A significant positive relationship was found between the mean amount of pins (A) and pounces (B) during the eight conditioning sessions of social play-induced conditioned place preference with the difference between time spent in the social compartment and the time spent in the non-social compartment during the preference test (pins: r_s = 0.66, p= 0.04; pounces: r_s = 0.73, p= 0.02). No significant correlation was found between the mean amount of social exploration during conditioning sessions and difference between the time spent in the social compartment and the time spent in the non-social compartment during the preference test (C: r_s = −0.37, p= 0.29). In addition, there was a significant positive relationship between the mean amount of being pinned and being pounced and the time spent in the social compartment (D: being pinned: r_s = 0.67, p= 0.03; being pounced: r_s = 0.64, p= 0.05, n=10). Data were analyzed using Spearman's correlation coefficient.

Figure 2. Effect of dopaminergic and noradrenergic drugs on social play-induced conditioned place preference (CPP)

Place conditioning was performed as previously described (Trezza et al., 2009; Achterberg et al., 2012, 2014b). (A) Methylphenidate (1–3 mg/kg) altered the acquisition of social play-induced CPP (F_compartment(1,114)=163.79, p<0.001; F_treatment(2,114)=0.01, p=0.99; F_{compartment × treatment}(2,114)=8.73, p<0.001; 0 mg/kg: n=34, 1.0 mg/kg: n=20, 3.0 mg/kg: n=10). At the lowest dose, it did not affect social play-induced CPP (0 mg/kg: t(33)=7.49, p<0.001; 1.0 mg/kg: t(19)=4.18, p=0.001), but treatment with 3 mg/kg methylphenidate increased the preference for the social compartment (3.0 mg/kg: t(9)=5.87, p=0.001; t(39)_soc0-soc3=−2.64, p=0.01; t(39)_nsoc0-nsoc3=2.33, p=0.03). (B) Cocaine (10 mg/kg) did not affect the acquisition of social play-induced CPP. The animals showed a preference for the social compartment (F_compartment(1,86)=61,77 p<0.001; F_treatment(1,86)=0.50, p=0.48; F_{compartment × treatment}(1,86)=0.08, p=0.78; 0 mg/kg: n=24, 10 mg/kg: n=10). (C) The acquisition of social play-induced CPP was not affected by treatment with the dopamine receptor antagonist α-flupenthixol (F_compartment(1,104)=42.89, p<0.001; F_treatment(3,104)=0.24, p=0.85; F_{compartment × treatment}(3,104)=0.97, p=0.41; 0 mg/kg: n=24, 0.125 mg/kg: n=12, 0.25 mg/kg: n=10, 0.5 mg/kg: n=10) (D) The acquisition of social play-induced CPP was blocked by treatment with the dopamine reuptake inhibitor GBR-12909 (F_compartment (1,40)=12.65, p=0.001; F_treatment(1,40)<0.001, p=0.99; F_{compartment × treatment}(1,40)=4.630, p=0.04; t(11)_{social compartment -non-social compartment 0 mg/kg}=2.88, p=0.01; t(9)social compartment -non-social compartment 10 mg/kg=0.77, p=0.46; 0 mg/kg: n=12, 10 mg/kg: n=10). (E) Treatment with the noradrenaline reuptake inhibitor atomoxetine did not affect the acquisition of social play-induced CPP (F_compartment (1,70)=28.05, p<0.001; F_treatment(2,70)=0.20, p=0.82; F_{compartment × treatment}(2,70)=0.73, p=0.49; 0 mg/kg: n=18, 1.0 mg/kg: n=10, 3.0 mg/kg: n=10). Data are shown as mean+SEM, social compartment vs non-social compartment: *p<0.05, ***p<0.001. Time spent in social compartment, 0 mg/kg vs 3.0 mg/kg methylphendiate $p<0.05; time spent in non-social compartment, 0 mg/kg vs 3.0 mg/kg methylphenidate #p<0.05. Data were analysed using a two-way analysis of variance (ANOVA) with compartment and treatment as between subject effects. When appropriate, ANOVA was followed up by Student's paired t-tests.