Cannabinoid-dopamine interactions: Modulation of midbrain DA neurons by endocannabinoids

摘要: A key feature of human and animal behavior is to learn from environmental stimuli adapt efficiently. Under physiological conditions, dopaminergic (DA) neurons are used evaluate new sensory information adjust maximize reward minimize aversive consequences. The two main DA pathways in the mesencephalon originate substantia nigra pars compacta (SNpc) ventral tegmental area (VTA). Both vivo vitro studies have established that exhibit spontaneous spike firing driven by intrinsic electrophysiological properties, with their activity modulated afferent inputs a number neuromodulators, including endocannabinoids. In VTA SNpc, cannabinoid type 1- (CB1) ionotropic transient receptor potential vanilloid 1 (TRPV1) receptors abundantly expressed as well endogenous ligands, mainly anandamide 2-arachidonoylglycerol. This chapter attempts summarize some major research findings demonstrating SNpc vary significantly molecular properties according target location, endocannabinoids act on GABAergic, glutamatergic cholinergic terminals participate discrete mechanisms aimed at cell homeostatic regulation. As result, given role endocannabinoid system modulating neuronal function VTA, they might take part associative learning, signaling, goal directed behavior, motor skill learning action-habit transformation. These considerations help explaining correlation between an unbalanced signal altered DA-dependent processes underpinning diverse pathological conditions both nigrostriatal mesocorticolimbic systems.