Dissociating the role of endocannabinoids in the pleasurable and motivational properties of social play behaviour in rats

Abstract

Social play behaviour is a vigorous form of social interaction, abundant during the juvenile and adolescent phases of life in many mammalian species, including humans. Social play is highly rewarding and it is important for social and cognitive development. Being a rewarding activity, social play can be dissociated in its pleasurable and motivational components. We have previously shown that endocannabinoids modulate the expression of social play behaviour in rats. In the present study, we investigated whether endocannabinoids modulate the motivational and pleasurable properties of social play behaviour, using operant and place conditioning paradigms, respectively. Treatment with the anandamide hydrolysis inhibitor URB597 did not affect operant responding or social play-induced conditioned place preference (CPP) when administered at a dose (0.1mg/kg) known to increase the expression of social play behaviour, while it modestly reduced operant responding at a higher dose (0.2mg/kg). The cannabinoid-1 (CB1) receptor antagonist rimonabant reduced operant responding when administered at a dose (1mg/kg) known to decrease the expression of social play behaviour, although this effect may be secondary to concurrent drug-induced stereotypic behaviours (i.e., grooming and scratching). These data demonstrate that enhancing endocannabinoid levels does not differentially affect the motivational and pleasurable aspects of social play behaviour, whereas CB1 receptor blockade reduces the motivational aspects of social play behaviour, possibly due to response competition. Thus, endocannabinoids likely drive the expression of social play behaviour as a whole, without differentially affecting its motivational or pleasurable properties.

Keywords: Endocannabinoids; Operant conditioning; Place conditioning; Rimonabant; Rimonabant (Pubmed Chem CID: 104849); Social play behaviour; URB597; URB597 (Pubmed Chem CID: 1383884).

Figure 1. Effect of the FAAH inhibitor URB597 on responding for social play behaviour: influence of dose, isolation period and treatment of the stimulus animal

Experimental rats treated with the FAAH inhibitor URB597 (0.05–0.1–0.2 mg/kg, n=8) and given the opportunity to interact with an untreated stimulus partner upon lever pressing following a 24 h isolation period showed reduced active responses (A) and rewards obtained (B) at the highest dose tested, with no changes in inactive responses (A) and a tendency towards a reduced breakpoint (C). In a separate experiment (n=8), rats treated with URB597 (0.1 mg/kg) were given the opportunity to interact with a URB597-treated stimulus partner upon lever pressing following a 2 h isolation period. No effect of treatment with URB597 was observed, while reducing the isolation time (soc iso) from 24 hours to 2 hours before testing decreased the number of active responses and tended to reduce the rewards obtained, without affecting inactive responses or the breakpoint (D,E,F). Data are represented as mean+SEM. ^#0.08>p>0.05 (trend), *p<0.05, relative to vehicle (0 mg/kg URB597/24h social isolation) treatment.

Figure 2. Treatment with URB597 (0.1 mg/kg) did not alter social play-induced CPP (A) and did not induce CPP by itself (B)

(A) Data represent the mean time (sec + SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during a 15 min session. Both vehicle-treated animals (n = 16) and URB597-treated animals (0.1 mg/kg, n = 17) showed a significant preference for the social-play associated compartment. (B) Data represent the mean time (sec + SEM) spent in the compartment where animals received vehicle (white bars) and the compartment where animals received URB597 (grey bar) during a 15 min session. URB597 did not induce conditioned place preference or aversion.

Figure 3. Effects of the CB1 receptor antagonist rimonabant on responding for social play behaviour

Treatment with rimonabant (0.1–0.3–1.0 mg/kg, n=8) reduced active responses (A) and rewards obtained (B) at the highest dose tested, did not affect inactive responses (A) and tended to reduce the breakpoint (C). The percentage of time spent scratching was increased by the two highest doses of rimonabant (D). Data is represented as mean+SEM. ^#0.08>p>0.05, *p<0.05, relative to vehicle (0 mg/kg rimonabant) treatment.

Figure 4. Effects of the CB1 receptor antagonist rimonabant on social play-induced place conditioning

Data represent the mean time (sec + SEM) spent in the social compartment (grey/black bars) and the non-social compartment (white bars) during a 15 min session. Vehicle-treated animals (2 ml/kg, n = 12) and rimonabant-treated animals (0.1 mg/kg, n=12, 0.3 mg/kg, n=12) showed a significant preference for the social-play associated compartment..