Endocannabinoid and nitric oxide interactions in the brain

Endogenous cannabinoids (eCBs) and nitric oxide (NO) are classical retrograde transmitters that modulate synaptic function throughout the brain. Although much is known about how these signals individually control synaptic activity and behavior, accumulating evidence suggests that they can also interact in a multitude of ways in the brain and beyond. Here, we present evidence for interactions between endogenous cannabinoids and nitric oxide in the brain. Specifically, we describe the effects of eCBs on NO synthesis and downstream signaling and in turn, we discuss how NO alters eCB levels and signaling pathways. We also provide an overview on how these transmitters work together or in opposition at the same synapses. This information will further our understanding of how two important, ubiquitous signals interact in the brain to ultimately affect neural function and behavior. Because eCBs and NO are involved in many physiological and pathological phenomena, understanding how these transmitters interact in non-human animals could lead to important therapeutic interventions in humans that potentially target both systems.