These results indicate that -opioid receptors in the NAc mediate the rewarding properties of interpersonal interaction in adolescent rats
These results indicate that -opioid receptors in the NAc mediate the rewarding properties of interpersonal interaction in adolescent rats. < 0.01 versus vehicle/vehicle; #< 0.05, ##< 0.01 versus vehicle/morphine (Tukey's test; = 6C14 per treatment group). Histological confirmation of injection sites Injection sites were verified according to the process explained by Mahler et al. (2007) and Simmons and Self (2009). After screening, animals were killed by carbon dioxide inhalation and microinjected with 0.3 l of black ink over 60 s through the guide cannulae. Animals were immediately decapitated, and their brains were removed. Slices (20 m solid) were collected throughout the forebrain and analyzed under a dissecting microscope for the location of the infusion sites according to the atlas of Paxinos and Watson (2007). Only pairs in which both animals experienced bilateral needle songs terminating into the target area and no damage to the target tissues were included in the final analysis. Statistical analysis Pinning and pouncing frequencies and time spent in interpersonal exploration are expressed as mean SEM. To assess the effects of single treatments on interpersonal play behavior, data were analyzed using either one-way ANOVA followed by Tukey's test, or Student's test. To assess the effects of combined treatments on interpersonal play behavior, data were analyzed using two-way ANOVA, followed by Tukey's test. Horizontal locomotor activity was expressed as mean SEM traveled distance (in centimeters/15 min). The effects of drug treatment on locomotor activity were analyzed with a one-way repeated-measures ANOVA. Social play-induced conditioned place preference (CPP) data were expressed as mean SEM time spent in the social-paired and non-social-paired compartments around the test day, and analyzed by a paired Student test. Results Opioid receptors in the NAc are necessary and sufficient for morphine to increase interpersonal play behavior First, we tested the effects of intra-NAc infusion of morphine (0.05C0.1 g/0.3 l; = 6C14 per treatment group) on interpersonal play behavior in adolescent rats. Morphine, infused into the NAc at the dose of 0.1 g/0.3 l, increased pinning (< 0.001) (Fig. 1< 0.001) (Fig. 1= 0.58; NS) (Fig. 1= 2.11; NS) (Fig. 1= 6 per treatment group). Table 1. Intra-NAc infusion of morphine (0.05C0.1 g/0.3 l), DAMGO (0.1C10 ng/0.3 l), CTAP (0.3C3 g/0.3 l), and -endorphin (0.01C1 g/0.3 l) had no effect on interpersonal exploration = 1.24, NS????Morphine (0.05 g/0.3 l)42 7????Morphine (0.1 g/0.3 l)55 5Vehicle34 4= 1.3, NS????DAMGO (0.1 ng/0.3 l)28 4????DAMGO (1 ng/0.3 l)29 5????DAMGO (10 ng/0.3 l)40 5Vehicle39 6= 1.24, NS????CTAP (0.3 g/0.3 l)45 10????CTAP (3 g/0.3 l)40 5Vehicle51 8= 0.5, NS????-Endorphin (0.01 g/0.3 l)42 4????-Endorphin (0.1 g/0.3 l)48 4????-Endorphin (1 LXR-623 g/0.3 l)52 8 Open in a separate windows Data represent mean LXR-623 SEM time spent in interpersonal exploration. = 6C14 per treatment group. Intra-NAc infusion of a dose of the opioid receptor antagonist naloxone (0.5 g/0.3 l) that did not affect interpersonal play by itself, completely blocked the effects of systemic morphine treatment (1 mg/kg, s.c.) on interpersonal play [pinning: < 0.001; < 0.05 (Fig. 1< 0.001; < 0.001; < 0.001 (Fig. 1= 7C10 per treatment group]. analysis showed that morphine increased interpersonal play in rats that received intra-NAc vehicle, but not in animals that received intra-NAc naloxone. These results show that activation of opioid receptors within the NAc is necessary and sufficient for morphine to increase interpersonal play behavior. Opioid effects on interpersonal play are LXR-623 mediated through -opioid receptors in the NAc Morphine and naloxone are moderately selective for -opioid receptors, but they have considerable affinity for – and -opioid receptors as well (Goldstein kalinin-140kDa and Naidu, 1989; Mansour et al., 1995). High densities of -, -, and -opioid receptors are found in the NAc (Mansour et al., 1988; Le Merrer et al., 2009). Therefore, we next decided the contribution of NAc -, -, and -opioid receptors in interpersonal play, by screening the effects of intra-NAc infusion of selective agonists for -, -, and -opioid receptors. Intra-NAc infusion of the -opioid receptor agonist DAMGO (0.1C10 ng/0.3 l; = 8C11 per treatment group) increased pinning (< 0.001) (Fig. 2< 0.001) (Fig. 2= 8C10 per treatment group) experienced no effects on interpersonal play [pinning: = 6C9 per treatment group) decreased interpersonal play behavior [pinning: < 0.01 (Fig. 2< 0.01 (Fig. 2< 0.05, **< 0.01 versus vehicle (Tukey's test; = 7C8 per treatment group). To determine whether endogenous opioids acting on -opioid receptors mediate interpersonal play under physiological conditions, we investigated.