Cannabinoid modulation of the cortical information processing through the basal ganglia circuits in physiological and hypodopaminergic states

Abstract

The basal ganglia (BG) are a network of subcortical nuclei that classically have been considered to be involved in motor behaviours, with mounting evidence in the last decades indicating that they are also involved in cognitive and emotional processing. The BG nuclei are involved in several pathologies such as Parkinson's disease, where the dopaminergic (DA) system, that influences BG function, is seriously affected. The endocannabinoid system, especially the CB1 receptor, is highly expressed in the BG representing a promising therapeutic target in disorders related with these structures. The objective of this thesis was to characterize the CB1 receptor modulation on the sensorimotor and medial prefrontal BG circuits, as well as the impact of DA denervation upon them, using electrophysiological techniques. In this work, cortical information cross through both BG circuits differently, in a way that was affected by DA denervation. Moreover, the CB1 receptor is able to modulate information transmission through both BG circuits differently. Further assessment on the role of the role of the CB1 receptor on these circuits revealed that it specially influences cortico-striatal transmission through the SM circuits. After DA denervation, the ability of the CB1 receptor to modulate transmission was generally lost in both circuits, although there were no changes in the density of this receptor in the BG nuclei. This data contribute to increase our understanding of BG function, and the role of the endocannabinoid system in modulating BG circuits, in physiological and hypodopaminergic states. Hence, providing further evidence on the potential of the endocannabinoid system as a pharmacological target in pathologies with BG dysfunction such as Parkinson's disease.