Role of endogenous cannabinoids in the control of basal ganglia activity

Abstract

The cannabinoid system is a novel intercellular signaling system that plays a prominent role, among others, in the control of basal ganglia function. This finding can be concluded from the data obtained in different series of anatomical, biochemical, electrophysiological and pharmacological studies. These data demonstrated: (i) that the basal ganglia contain high levels of endocannabinoids and their receptors, mainly including the cannabinoid CB1 receptor subtype but also a related receptor type, the vanilloid TRPV1 receptor; (ii) that the activation or the blockade of this system produces important changes in motor behavior, changes that are originated as a consequence of interactions of the cannabinoid system with various classic neurotransmitters such as GABA, dopamine or glutamate; and (iii) the occurrence of marked changes in specific elements of the cannabinoid signaling system in various basal ganglia disorders, with emphasis in the induction/upregulation of the cannabinoid CB2 receptor subtype. This large evidence relating endocannabinoids and their receptors to the function of the basal ganglia, both in the healthy and the pathological brain, has provided support for the idea that cannabinoid-based medicines, with selectivity for different targets of the cannabinoid signaling system (synthetic enzymes, receptors, inactivation system), might have therapeutic potential to alleviate symptoms and/or provide neuroprotection in basal ganglia disorders, in particular Parkinson´s disease and Huntington´s chorea. The present chapter will review the knowledge on this issue trying to establish the future lines for the research on the therapeutic potential of the cannabinoid signaling system in basal ganglia disorders.