Sex differences in monoamines following amphetamine and social reward in adolescent rats.

Abstract

Interaction with social peers may increase rates of drug self-administration, but a recent study from our laboratory showed that social interaction may serve as a type of alternative reward that competes with drug taking in adolescent male rats. Based on those previous results, the current study examined sex differences in preference for social interaction compared to amphetamine (AMPH) in adolescent rats using the conditioned place preference (CPP) paradigm. Similar to previous results with males, females showed AMPH CPP regardless whether they were individual- or pair-housed. In contrast to males, however, females failed to show social CPP, and they did not prefer a peer-associated compartment over an AMPH-associated compartment in a free-choice test. In separate experiments, dopamine (DA) and serotonin (5-HT) metabolite levels were measured in adolescent males and females that were exposed acutely to peer interaction, no peer interaction, AMPH, or saline. In amygdala, levels of the DA metabolite dihydroxyphenylacetic acid (DOPAC) were altered more in response to peer interaction in males than females; in contrast, there was a greater amygdala DOPAC response to AMPH in females. Furthermore, there were greater changes in the 5-HT metabolite 5-HIAA in females than in males following social interaction. These results indicate that the ability of peer interactions to reduce drug reward is greater in adolescent males than females, perhaps due to a greater ability of social cues to activate limbic reward mechanisms in males or a greater ability of AMPH cues to activate limbic reward mechanisms in females.

Sex-dependent regulation of social reward by oxytocin receptors in the ventral tegmental area

“…Social stimuli can also trigger greater dopamine release in females than males, as shown in rats exposed to same-sex stimulus animals after a period of social isolation [32]. In female rats, the levels of the dopamine metabolite DOPAC in the striatum were higher during same-sex social interactions, whereas in males no changes in DOPAC levels were observed [33]. Similar sex differences have also been found in humans [34].…”

Sex-dependent regulation of social reward by oxytocin: an inverted U hypothesis

“…For example, social stimuli might trigger greater DA release in females than males, as shown among control groups in a study of rats exposed to same-sex stimulus animals after a period of social isolation [86]. Furthermore, in female rats, DOPAC (DA metabolite) levels in the striatum were elevated during same-sex social interactions, while in males no difference in DOPAC levels were observed [123]. In addition, social housing can reduce drug intake in operant conditioning models, compared to social isolation housing [124][125][126][127], an effect that is more consistent in females than in males and may be mediated by OT in mesolimbic regions [128,129].…”

Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females

“…Many of these changes are sex-specific. Adolescent male rats exhibit a greater preference for social stimuli in a conditioned place preference (CPP) test when compared to adults (Douglas et al, 2004; Yates et al, 2013) or to females (Douglas et al, 2004; Weiss et al, 2015). Male rodents also place a greater value on peer-directed activities including play behaviors (Pellis and Pellis, 2017).…”

“…However, it is important to note that this effect is most pronounced in males deprived of social interactions. Additionally, a peer-paired chamber negates cocaine (Zernig et al, 2013) and amphetamine (Yates et al, 2013) induced CPP in adolescent males but not females (amphetamine only; Weiss et al, 2015). These data suggest that there are striking sex differences in responses to social reward in adolescent rodents with males displaying a greater sensitivity to social reward than females.…”