The Endocannabinoid System in the Physiology and Pathology of the Basal Ganglia

Multiple lines of evidence indicate a prominent role for the cannabinoid signaling system in the control of basal ganglia function, exerted by modulating the activity of various classic neurotransmitters, such as GABA, dopamine, or glutamate, that operate within this circuit. Throughout the basal ganglia, the activity-evoked release of endocannabinoids has been found to directly regulate the release and plas- ticity of both excitatory and inhibitory synapses. These observations, together with the demonstration that different elements (receptors, ligands, enzymes) of the can- nabinoid signaling system are markedly disturbed in basal ganglia disorders, namely Parkinson's and Huntington's disease, provide support to the idea that cannabinoid- based medicines, with selectivity for different targets of the cannabinoid signaling system, might have therapeutic benefits in these disorders. These benefits would include the alleviation of specific motor symptoms but they could be also extended to a possible delay or arrest of disease progression based on the neuroprotective and/or neuroregenerative properties of certain cannabinoid compounds. In this chapter we review the anatomical, neurochemical, electrophysiological, and pharmacological bases that sustain the importance of the cannabinoid system in basal ganglia function, attempting also to present current information and future lines for research on the therapeutic potential of this system in basal ganglia disorders.