Effects of cocaine combined with a social cue on conditioned place preference and nucleus accumbens monoamines after isolation rearing in rats

Abstract

Rationale: Social interaction during drug exposure can potentiate cocaine reward. Isolation rearing (ISO) during adolescence increases social interaction and may amplify this potentiation.

Objectives: The objectives of this study are to determine whether ISO alters conditioned place preference (CPP) for cocaine when combined with a social cue and to determine whether ISO alters the effects of cocaine when combined with social cue on nucleus accumbens shell (NAcS) dopamine (DA) and serotonin (5-HT).

Methods: Male and female rats were either ISO or 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 interaction 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 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.

Fig. 1. Timelines of the CPP (a, top) and microdialysis (b, bottom) experiments

Fig. 2

Representative microdialysis probe placements in the NAcS. Left: photomicrographs of cresyl violet stained probe tracks in the NAcS with midline (ML) and anterior commissure (AC) as landmarks. Right Image adapted from Paxinos and Watson (2007) showing representative placements. Values on the right indicated distance from bregma. Not all 113 placements are shown due to overlapping placements

Fig. 3

Dose dependent effects of cocaine on social interaction with a novel conspecific in male rats. Values represent the total amount of time (s, means±SEMs) that experimental rats spent actively engaged in social interaction with a novel conspecific during a 10 min trial. ** p< .01, less than saline; ##p< .01, <2 mg/kg cocaine

Fig. 4

Conditioned place preference (CPP) to cocaine (2 mg/kg) with or without a social cue in isolation reared (ISO) and group-reared (GRP) female (top) and male (bottom) rats. Values represent difference scores: time (s, means±SEMs) spent in the drug/social cue-paired chamber posttest minus time spent in that chamber pretest. #p<.05, *p<.01, difference scores significantly different from the hypothesized mean of 0

Fig. 5

Social behavior with a novel same-sex conspecific during the conditioning trials in rats exposed to a social cue during place preference, averaged across both paired trials. a Time (s) engaged in social interaction. b Time (s) spent in aggressive grooming by the experimental rat. Cocaine reduced aggressive grooming overall (main effect of drug, p<.001). c Pinning (number of pins) by the experimental rat. * p< .05, less than ISO saline

Fig. 6

DA in the NAcS of GRP (a, c) and ISO (b, d) male and female rats exposed to cocaine either in the presence or absence of a social cue. Cocaine produced increases in NAcS DA regardless of the presence or absence of a social cue in GRP rats (a, c). Cocaine produced increases in NAcS DA only in the presence of a social cue in ISO rats (b, d). The arrows indicate injection of either saline or 2 mg/kg cocaine, and the horizontal bars indicate the presence of a novel same-sex conspecific in the dialysis chamber. *p<.05, GRP rats with cocaine with or without a social cue different from GRP rats with saline, with or without social experience, at this time point. #p<.05, ISO rats with cocaine and social cue different from all other ISO groups at this time point

Fig. 7

5-HT in the NAcS of GRP (a, c) and ISO (b, d) male and female rats exposed to cocaine either in the presence or absence of a social cue. Cocaine and a social cue interacted to increase NAcS 5-HT preferentially in male ISO rats. The arrows indicate injection of either saline or 2 mg/kg cocaine, and the horizontal bars indicate the presence of a novel same-sex conspecific in the dialysis chamber. $ p<.01, ISO males with cocaine and social cue different from all other groups at this time point