Neural correlates of MDMA (“Ecstasy”)-induced social interaction in rats

MDMA (Ecstasy) produces feelings of love and closeness in humans and prosocial effects in animals. In male Wistar rats, a moderate dose (5 mg/kg) increased social interaction, specifically general investigation of other rats while decreasing anogenital sniffing. Analysis of neural activation across 39 brain regions showed that MDMA given in a social context caused considerably greater brain activation than the same dose given to solitary rats. Six brain regions—including the caudate-putamen, medial preoptic area, paraventricular thalamic nucleus, central amygdala, ventromedial hypothalamic nucleus, and medial amygdala—showed augmented activation in the social-MDMA group. The nucleus accumbens, ventral tegmental area, and periaqueductal grey were activated only when MDMA was combined with social interaction. These findings suggest MDMA modulates neural circuits regulating affiliative behavior, possibly via oxytocin.

Study at a glance

Abstract

The popular drug 3,4 methylenedioxymethamphetamine (MDMA, "Ecstasy", "the Love Drug") produces feelings of love and closeness in humans and induces analogous prosocial and antiaggressive effects in laboratory animals. Here we examined the specific brain regions that may be involved in these prosocial effects. Male Wistar rats were pretreated with a moderate dose of MDMA (5 mg/kg) or vehicle and then either kept alone in a familiar test chamber for 60 min (groups MDMA-ALONE and VEHICLE-ALONE) or allowed to engage in social interaction in the familiar test chamber with an unfamiliar same-sex conspecific for 60 min (groups MDMA-SOCIAL and VEHICLE-SOCIAL). Rats in the MDMA-SOCIAL group showed much greater overall social interaction than rats in the VEHICLE-SOCIAL group, with microanalysis revealing increased general investigation of other rats but decreased anogenital sniffing. Analysis of neural activation across 39 brain regions using Fos immunohistochemistry showed the following results: (1) VEHICLE-SOCIAL and VEHICLE-ALONE groups did not differ in Fos expression, indicating that a social context per se did not affect Fos expression, (2) MDMA-treated groups showed significantly increased Fos expression relative to VEHICLE treated groups in 30 brain regions, (3) the MDMA-SOCIAL group showed augmented Fos expression relative to the MDMA-ALONE group in six brain regions including the caudate-putamen (medial), medial preoptic area, paraventricular thalamic nucleus, central amygdala, ventromedial hypothalamic nucleus, and the medial amygdala (posterodorsal), and (4) the MDMA-SOCIAL group (but not the MDMA-ALONE group) showed augmented Fos expression relative to the VEHICLE groups in the nucleus accumbens, ventral tegmental area and periaqueductal grey. These results indicate that a moderate dose of MDMA given in a social context causes considerably greater brain activation than the same dose given to solitary rats. This activation involves specific neural circuits that are known to regulate affiliative behavior, perhaps by modulating the incentive value of social stimuli. A possible role for the neuropeptide oxytocin in mediating the prosocial effects of MDMA is discussed.