Abstract
Endocannabinoids released during cerebral ischemia have been implicated as neuroprotective agents. We assessed the role of cannabinoid receptors in modulating the response of neurons to oxygen/glucose deprivation (OGD), a model for in vitro ischemia, in rat hippocampal slices using extracellular recording techniques. Under control conditions, 15 min OGD resulted in only 50% recovery of CAI field excitatory postsynaptic potentials (fEPSPs) 60 min post-insult. This post-OGD depression of function was primarily NMDA receptor-dependent as the NMDA receptor antagonist MK-801 (50 mu M) promoted recovery of synaptic transmission to 76% of the baseline. Treatment with the CB1 receptor antagonist AM251 (1 mu m), which prevented the depression of excitatory synaptic transmission caused by WIN55,212-2 (1 mu M), also markedly enhanced recovery of function (71% of control). The enhanced recovery after OGD in the presence of AM251 was independent of both GABA(A) receptors and NMDA receptors since co-application of AM251 with either bicuculline (10 mu M) or MK-801 (50 mu M) did not alter recovery, or further improved recovery, respectively. These results suggest endocannabinoids released during OGD may modulate synaptic transmission and post-OGD neuronal outcome via activation of an AM251-sensitive cannabinoid receptor. (C) 2007 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 1327-1335 |
Number of pages | 9 |
Journal | Neuropharmacology |
Volume | 52 |
Issue number | 6 |
DOIs | |
Publication status | Published - May 2007 |
Keywords
- hypoxia
- oxygen/glucose deprivation
- anoxic depolarisation
- cannabinoids
- endocannabinoids
- NMDA receptors
- ischemia
- IN-VITRO ISCHEMIA
- CULTURED CORTICAL-NEURONS
- CEREBELLAR CB1 RECEPTOR
- FOCAL CEREBRAL-ISCHEMIA
- LONG-TERM POTENTIATION
- SYNAPTIC-TRANSMISSION
- GABAERGIC TRANSMISSION
- ENDOCANNABINOID SYSTEM
- MOTOR INCOORDINATION
- BRIEF ANOXIA