title: Protective activation of the endocannabinoid system during ischemia in dopamine neurons.
abstract: Endocannabinoids act as neuroprotective molecules promptly released in response to pathological stimuli. Hence, they may represent one component of protection and/or repair mechanisms mobilized by dopamine (DA) neurons under ischemia. Here, we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) plays a key role in protecting DA neurons from ischemia-induced altered spontaneous activity both in vitro and in vivo. Accordingly, neuroprotection can be elicited through moderate cannabinoid receptor type-1 (CB1) activation. Conversely, blockade of endocannabinoid actions through CB1 receptor antagonism worsens the outcome of transient ischemia on DA neuronal activity. These findings indicate that 2-AG mediates neuroprotective actions by delaying damage and/or restoring function of DA cells through activation of presynaptic CB1 receptors. Lastly, they point to CB1 receptors as valuable targets in protection of DA neurons against ischemic injury and emphasize the need for a better understanding of endocannabinoid actions in the fine control of DA transmission.
authors.affiliation: Centre of Excellence Neurobiology of Addiction, University of Cagliari, Italy. myriam@unica.it
authors.forename: Miriam
authors.initials: M
authors.lastname: Melis
authors.forename: Giuliano
authors.initials: G
authors.lastname: Pillolla
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Alberto
authors.initials: A
authors.lastname: Minassi
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Simona
authors.initials: S
authors.lastname: Perra
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Muntoni
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002545:Brain Ischemia / Q000503:physiopathology*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D000077285:Rimonabant; D015398:Signal Transduction / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000503:physiopathology; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D004298:Dopamine; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D000099252:Fatty Acid Amide Hydrolases; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C094503:glyceryl 2-arachidonate; C109925:AM 281