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

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    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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