Cannabinoid modulation of dopaminergic circuits in neurodegenerative and neuropsychiatric disorders

The endocannabinoid system timely orchestrates a variety of cerebral physiological processes by modulating brain neurotransmitters, and in particular the dopamine system. Both endocannabinoid and dopamine receptors are highly abundant and often coexpressed in the basal ganglia and mesolimbic pathways, where they regulate motor functions and motivational aspects of behavior. Understanding the interrelationship between these two systems is crucial to gain new insight on the pathophysiology of brain disorders characterized by a dysregulation of dopamine, such as Parkinson's disease and schizophrenia. This review aims at: (1) presenting the complex functional interactions between these two neurotransmitter systems at the anatomical, pharmacological, cellular and electrophysiological levels, and (2) addressing the contribution of disturbances of cannabinoid-dopamine interactions to neurodegenerative and psychiatric disorders.