title: Hub and switches: endocannabinoid signalling in midbrain dopamine neurons.
abstract: The last decade has provided a wealth of experimental data on the role played by lipids belonging to the endocannabinoid family in several facets of physiopathology of dopamine neurons. We currently suggest that these molecules, being intimately connected with diverse metabolic and signalling pathways, might differently affect various functions of dopamine neurons through activation not only of surface receptors, but also of nuclear receptors. It is now emerging how dopamine neurons can regulate their constituent biomolecules to compensate for changes in either internal functions or external conditions. Consequently, dopamine neurons use these lipid molecules as metabolic and homeostatic signal detectors, which can dynamically impact cell function and fitness. Because dysfunctions of the dopamine system underlie diverse neuropsychiatric disorders, including schizophrenia and drug addiction, the importance of better understanding the correlation between an unbalanced endocannabinoid signal and the dopamine system is even greater. Particularly, because dopamine neurons are critical in controlling incentive-motivated behaviours, the involvement of endocannabinoid molecules in fine-tuning dopamine cell activity opened new avenues in both understanding and treating drug addiction. Here, we review recent advances that have shed new light on the understanding of differential roles of endocannabinoids and their cognate molecules in the regulation of the reward circuit, and discuss their anti-addicting properties, particularly with a focus on their potential engagement in the prevention of relapse.
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, C.N.R. Neuroscience Institute, 09042 Monserrato, Cagliari, Italy. myriam@unica.it
authors.forename: Miriam
authors.initials: M
authors.lastname: Melis
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009042:Motivation; D009422:Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D009538:Nicotine / Q000009:adverse effects / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D012201:Reward; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D009435:Synaptic Transmission
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; D018079:Receptors, GABA; D009538:Nicotine; C094503:glyceryl 2-arachidonate; D004298:Dopamine