6533b85efe1ef96bd12bfd1e

RESEARCH PRODUCT

Protective activation of the endocannabinoid system during ischemia in dopamine neurons

Simona PerraGian Luigi GessaBeat LutzStefania PetrosinoMiriam MelisAnna Lisa MuntoniGiovanni MarsicanoMarco PistisVincenzo Di MarzoTiziana BisognoAlberto MinassiGiuliano Pillolla

subject

MaleCannabinoid receptorDopaminePharmacologyBrain IschemiaMidbrainRats Sprague-DawleyMicePiperidinesReceptor Cannabinoid CB1IschemiaPremovement neuronal activityReceptorMice KnockoutNeuronsmusculoskeletal neural and ocular physiologyEndocannabinoid systemCB1NeuroprotectionElectrophysiologyNeurologylipids (amino acids peptides and proteins)Rimonabantpsychological phenomena and processesmedicine.drugSignal TransductionMorpholinesIschemiaArachidonic AcidsBiologyIn Vitro TechniquesNaphthalenesNeuroprotectionAmidohydrolasesGlycerideslcsh:RC321-571DopamineCannabinoid Receptor ModulatorsmedicineAnimalslcsh:Neurosciences. Biological psychiatry. NeuropsychiatryEndocannabinoidVentral Tegmental Areamedicine.diseaseBlockadeBenzoxazinesRatsnervous systemPyrazolesNeuroscienceEndocannabinoids

description

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.

yearjournalcountryeditionlanguage
2006-10-01Neurobiology of Disease
10.1016/j.nbd.2006.04.010http://www.sciencedirect.com/science/article/pii/S0969996106000982