Post-weaning social isolation (PSI) has been shown to increase aggressive behavior and alter medial prefrontal cortex (mPFC) function in rats. The present study sought to determine whether this phenotype would be normalized by increasing levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) using pharmacological inhibition of monoacylglycerol lipase (MAGL). Male and female Sprague-Dawley rats were exposed to either 4 weeks of PSI or social rearing (SR) starting on postnatal day 21, then underwent a 15 min trial of social interaction with a novel, same-sex juvenile rat. Rats were administered an acute injection of the MAGL inhibitor MJN110 or vehicle prior to the social interaction. Rats received either 0 mg/kg (vehicle), 1 mg/kg, or 5 mg/kg of MJN110. Both doses of MJN110 decreased aggressive grooming, a measure of agonistic behavior, in both males and females, largely driven by decreased aggressive grooming in PSI rats. There were no effects of MJN110 on overall social behavior or play behavior, while modest effects were observed on locomotor activity in SR rats only. While social interaction increased c-Fos expression in the mPFC of both males and females, MJN110 reduced c-Fos preferentially in females. These results suggest that 2-AG can modulate specific social behaviors during adolescence, and may affect mPFC function differentially in males and females.

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