Biology session

Previous studies showed that endocannabinoid signaling plays a role in the regulation of social behavior, predominantly aggression, although the details of this role are still to be clarified. Current pharmacological manipulations employed to study this issue result in a number of non-specific effects which possibly prevents the detailed description of the background mechanisms.

In the present study, we employ a more specific approach to manipulate endocannabinoid signaling. Using the agent JZL184, we blocked monoacylglycerol lipase in male CD1 mice, the degrading enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), which resulted in elevated levels and therefore enhanced signaling of 2-AG. We studied the effects of the above treatment on aggression in the resident-intruder paradigm. As previous studies showed that behavioral effects of enhanced 2-AG signaling depended on the experimental context, residents and intruders were both studied. Furthermore, measuring corticosterone levels we studied treatment effects on stress-reactivity and correlations between such effects and putative effects on behavior. Additionally, we assessed whether the effects depended on cannabinoid receptor type-1 (CB1) activity, as behavioral and physiological effects of 2-AG are reported to be mediated via this receptor.

JZL184 dramatically decreased the level of aggressiveness in a context independent manner both in resident and intruder animals. Furthermore it increased stress-reactivity in the case of the latter. Antiaggressive effects were independent of endocrine effects and CB1 activity, respectively.

Taken together, 2-AG was proved to be a strong negative modulator of aggressive behavior. As its effects occurred in a context-independent manner in contrast to its context-dependent effects on non-social behavior, one may suggest that its impact on social behavior is more specific and robust. Furthermore we report that the behavioral effects occur independently of effects on stress-reactivity, via a yet unidentified CB1 receptor-independent mechanism.