Modulation of Noradrenergic and Serotonergic Systems by Cannabinoids: Electrophysiological, Neurochemical and Behavioral Evidence.

The main noradrenergic and serotonergic nuclei in the central nervous system (CNS) are the locus coeruleus (LC) and the dorsal raphe nucleus (DRN). These brain areas, located in the brainstem, play a pivotal role in the control of various functions and behaviors that are altered by cannabinoids (i.e., pain, arousal, mood, anxiety, or sleep-wake cycle). Anatomical, neurochemical, and functional data suggest that cannabinoids regulate both central noradrenergic and serotonergic neurotransmission. Thus, strong evidence has shown that the firing activity of LC and DRN monoamine neurons or the synthesis/release of noradrenaline (NA) and serotonin (5-HT) in the projection areas are all affected by cannabinoid administration. Herein, we propose that interaction between the endocannabinoid system and the noradrenergic-serotonergic systems could account for some of the anxiolytic, antidepressant, and antinociceptive effects of cannabinoids or the disruption of attention/sleep induced by these drugs.