Endocannabinoid Signaling in the Control of Social Behavior

Abstract

Many mammalian species, including humans, exhibit social behavior and form complex social groups. Mechanistic studies in animal models have revealed important roles for the endocannabinoid signaling system, comprising G protein-coupled cannabinoid receptors and their endogenous lipid-derived agonists, in the control of neural processes that underpin social anxiety and social reward, two key aspects of social behavior. An emergent insight from these studies is that endocannabinoid signaling in specific circuits of the brain is context dependent and selectively recruited. These insights open new vistas on the neural basis of social behavior and social impairment. The crucial adaptive value of sociality is represented across evolutionary time. Modern techniques have been used to identify the neural circuits processing social information and regulating social behavior. The oxytocin system is now recognized as being central to such socially specific signaling. The plant Cannabis sativa has long been exploited to facilitate social bonding, and experimental studies have explored its psychotropic effects on human social behavior. Since the identification of the endocannabinoid signaling system, animal studies targeting cannabinoid receptors and transmitters [anandamide and 2-arachidonoyl-sn-glycerol (2-AG)] have found regulatory effects, particularly in social anxiety and social reward, as well as endocannabinoid dysregulation in social impairment related to neuropsychiatric conditions. These endocannabinoid effects are multimodal and context dependent. Newly identified oxytocin-driven endocannabinoid signaling potentially represents a circuit-based mechanism through which selective recruitment of endocannabinoid signaling can occur, and may underlie the differential actions of anandamide and 2-AG.