Strain- and context-dependent effects of the anandamide hydrolysis inhibitor URB597 on social behavior in rats.

Genetic and environmental factors play an important role in the cannabinoid modulation of motivation and emotion. Therefore, the aim of the present study was to test whether anandamide modulation of social behavior is strain- and context-dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and adult Wistar and Sprague-Dawley rats tested in different emotionally arousing conditions (familiarity/unfamiliarity to the test cage, low/high light). Under all experimental conditions, adolescent and adult Sprague-Dawley rats displayed higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats. URB597 enhanced social play behavior in adolescent Wistar rats under all experimental conditions. However, URB597 only increased social interaction in adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect adolescent social play behavior and adult social interaction in Sprague-Dawley rats under any experimental condition. Moreover, URB597 increased the USVs emitted during social interaction by adolescent Wistar and adult Sprague-Dawley rats tested under familiar/high light and unfamiliar/high light, respectively. These results show that anandamide has distinct roles in adolescent and adult social behaviors. Anandamide modulation of adolescent social play behavior is strain- but not context-dependent. Conversely, anandamide modulation of adult social behavior and USV emission depends upon both strain and experimental context. Furthermore, these results confirm that profound behavioral differences exist between Wistar and Sprague-Dawley rats, which may explain the sometimes contradictory effects of cannabinoid drugs on emotionality in different strains of rodents.