Cannabinoid modulation of neuronal function after oxygen/glucose deprivation in area CA1 of the rat hippocampus

Farid F. Youssef, Sheriar G. Hormuzdi, Andrew J. Irving, Bruno G. Frenguelli

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    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 languageEnglish
    Pages (from-to)1327-1335
    Number of pages9
    JournalNeuropharmacology
    Volume52
    Issue number6
    DOIs
    Publication statusPublished - 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

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