Rationale Social interaction during drug exposure can potentiate cocaine reward. group (GRP) reared for 4 weeks during adolescence. CPP was performed using a low dose of cocaine (2 mg/kg or saline) with or without exposure to a novel same-sex conspecific during conditioning. In vivo microdialysis was performed using the same parameters. Results ISO rats engaged in more social and aggressive behaviors during conditioning relative to GRP. Cocaine reduced social and aggressive behaviors in all rats. CPP was not influenced by rearing condition. Cocaine produced significant CPP and a social cue produced CPP only in males. In contrast the conversation of cocaine and a social cue on NAcS DA and 5-HT differed depending upon rearing condition. In isolates cocaine-induced DA was attenuated while Hydroxyfasudil hydrochloride Hydroxyfasudil hydrochloride cocaine plus a social cue produced potentiated DA and 5-HT. Conclusions Exposure to a low dose of cocaine in the presence of a social cue produced additive effects on CPP while producing synergistic effects on DA and 5-HT in the NAcS of ISO rats. The aversive effects of this compound stimulus may negate the rewarding effects in isolates. Image adapted from Paxinos and Watson (2007) showing … Statistical analysis Statistics were performed using PASW Statistics 18.0. Social exploration in the dose-response study was analyzed with one-way ANOVA. CPP data [difference scores: time spent in the paired chamber posttest minus pretest (s)] were analyzed using 2 (rearing)×2 (drug)×2 (sex)×2 (social cue) factorial ANOVA. In addition to assess whether place preference had occurred single-sample tests were performed on each group to determine whether the difference score was significantly different than 0. Behavioral data were analyzed using 2 (rearing)×2 (drug)×2 (sex) factorial ANOVA. Fisher’s least significant difference post hoc assessments were performed when significant interactions were observed. DA and 5-HT basal data (pg/40 μl sample) were analyzed using 2 (rearing)× 2 (Drug)×2 (sex)×2 (social cue) factorial ANOVA. DA and 5-HT (percent baseline) data were analyzed using mixed ANOVA with rearing drug sex and social cue as between-groups variables and time as a within subjects variable. Simple effects tests were performed post hoc at Hydroxyfasudil hydrochloride each time point when significant interactions with time were observed. Alpha was set at .05 for all those experiments. Results Dose dependency of cocaine’s effects on social exploration In order to determine the effects of three different doses of cocaine on social exploration we Hydroxyfasudil hydrochloride assessed the amount of time that group-reared late adolescent male rats spent actively engaged with a novel conspecific during 10-min trials. Cocaine dose dependently decreased the amount of time spent actively engaged in social exploration with higher doses having profoundly suppressive effects on social exploration (Fig. 3). One-way ANOVA revealed a highly significant effect of cocaine dose on social exploration [(3 12 (1 131 15.43 (1 131 (1 131 (1 31 (1 31 (1 31 (1 31 assessments indicated that significant CPP (significant difference from 0) was observed for cocaine alone in GRP males and females for social cue alone in GRP and ISO males and for cocaine plus social cue in GRP and ISO males and females. Fig. 4 Conditioned place preference ((1 65 (1 65 (1 65 (1 65 (1 65 (1 65 (1 65 (8 752 (1 89 (8 712 (8 712 (8 712 (1 81 (8 656 =2.27 [1 78 8.73 (8 624 (1 78 (8 624 indicate injection … Discussion We hypothesized that this increase in social exploration produced by 4 weeks of isolation rearing would potientiate both CPP for a social cue and CPP for a combined social cue and cocaine challenge and that this would be associated with potentiation of Hydroxyfasudil hydrochloride NAcS monoamines. MDA1 To explore this idea we used low doses of both social exposure (Calcagnetti and Schechter 1992; Douglas et al. 2004; Kummer et al. 2011) and cocaine. Here we report a dissociation between behavioral and neurochemical responses to a low dose of cocaine combined with a social cue in isolation-reared rats. We observed additive effects of the combination of social cue and cocaine reward on CPP that was not affected by rearing condition or by sex. However we observed synergistic effects of the combination of social cue and cocaine reward on both DA and 5-HT in the NAcS of isolation-reared rats. We were surprised that two conditioning trials with a social cue even in the absence of cocaine produced significant CPP and although this was most pronounced in males there was no impact of rearing condition..