Anatomical, biochemical, and behavioral evidence for cannabinoid modulation of noradrenergic circuits: role of norepinephrine in cannabinoid-induced aversion

Abstract

The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This chapter summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical and functional evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, the impact of this interaction with respect to specific behaviors is explored, demonstrating that norepinephrine is a critical determinant of cannabinoid-induced aversion, which adds another dimension to how central noradrenergic circuitry is regulated by the cannabinoid system.