Cannabinoid-dopamine interactions in the physiology and physiopathology of the basal ganglia.

Endocannabinoids and their receptors play a modulatory role in the control of dopamine transmission at the basal ganglia. However, this influence is generally indirect and exerted through the modulation of GABA and glutamate inputs received by nigrostriatal dopaminergic neurons, which lack of CB1 receptors although may produce endocannabinoids. Additional evidence suggest that CB2 receptors may be located in nigrostriatal dopaminergic neurons, as well as that certain eicosanoid-related cannabinoids may directly activate TRPV1 receptors, which have been found in nigrostriatal dopaminergic neurons, thus allowing in both cases a direct regulation of dopamine transmission by specific cannabinoids. In addition, CB1 receptors form heteromers with dopaminergic receptors which represent another way to make possible a direct interaction between both systems, in this case at the postsynaptic level. Through these direct mechanisms or through indirect mechanisms involving GABA or glutamate neurons, cannabinoids may interact with dopamine transmission in the basal ganglia and this likely has an important influence on dopamine-related functions in these structures (i.e. control of movement) and, particularly, on different pathologies affecting these processes, in particular, Parkinson’s disease, but also dyskinesia, dystonia and other pathological conditions. The present review will address the current literature supporting these cannabinoid-dopamine interactions at the basal ganglia, with emphasis in aspects dealing with the physiopathological consequences of these interactions.
This article is protected by copyright. All rights reserved.