Endocannabinoids and their receptors, mainly the CB(1) receptor type, function as a retrograde signaling system in many synapses within the CNS, particularly in GABAergic and glutamatergic synapses. They also play a modulatory function on
dopamine (DA) transmission, although CB(1) receptors do not appear to be located in dopaminergic terminals, at least in the major brain regions receiving dopaminergic innervation, e.g., the caudate-putamen and the nucleus accumbens/prefrontal cortex. Therefore, the effects of
cannabinoids on DA transmission and DA-related behaviors are generally indirect and exerted through the modulation of
GABA and
glutamate inputs received by dopaminergic neurons. Recent evidence suggest, however, that certain
eicosanoid-derived
cannabinoids may directly activate TRPV(1) receptors, which have been found in some dopaminergic pathways, thus allowing a direct regulation of DA function. Through this direct mechanism or through indirect mechanisms involving
GABA or
glutamate neurons,
cannabinoids may interact with DA transmission in the CNS and this has an important influence in various DA-related neurobiological processes (e.g., control of movement, motivation/reward) and, particularly, on different pathologies affecting these processes like
basal ganglia disorders,
schizophrenia, and
drug addiction. The present review will address the current literature supporting these
cannabinoid-DA interactions, with emphasis in aspects dealing with the neurochemical, physiological, and pharmacological/therapeutic bases of these interactions.