Protective activation of the endocannabinoid system during ischemia in dopamine neurons.

Miriam Melis, Giuliano Pillolla, Tiziana Bisogno, Alberto Minassi, Stefania Petrosino, Simona Perra, Anna Lisa Muntoni, Beat Lutz, Gian Luigi Gessa, Giovanni Marsicano
Neurobiology of Disease. 2006-10-01; 24(1): 15-27
DOI: 10.1016/j.nbd.2006.04.010

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1. Neurobiol Dis. 2006 Oct;24(1):15-27. Epub 2006 Jun 8.

Protective activation of the endocannabinoid system during ischemia in dopamine

Melis M(1), Pillolla G, Bisogno T, Minassi A, Petrosino S, Perra S, Muntoni AL,
Lutz B, Gessa GL, Marsicano G, Di Marzo V, Pistis M.

Author information:
(1)Centre of Excellence Neurobiology of Addiction, University of Cagliari, Italy.

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.

DOI: 10.1016/j.nbd.2006.04.010
PMID: 16762556 [Indexed for MEDLINE]

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