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

TY - JOUR

T1 - Cannabinoid modulation of neuronal function after oxygen/glucose deprivation in area CA1 of the rat hippocampus

AU - Youssef, Farid F.

AU - Hormuzdi, Sheriar G.

AU - Irving, Andrew J.

AU - Frenguelli, Bruno G.

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

KW - hypoxia

KW - oxygen/glucose deprivation

KW - anoxic depolarisation

KW - cannabinoids

KW - endocannabinoids

KW - NMDA receptors

KW - ischemia

KW - IN-VITRO ISCHEMIA

KW - CULTURED CORTICAL-NEURONS

KW - CEREBELLAR CB1 RECEPTOR

KW - FOCAL CEREBRAL-ISCHEMIA

KW - LONG-TERM POTENTIATION

KW - SYNAPTIC-TRANSMISSION

KW - GABAERGIC TRANSMISSION

KW - ENDOCANNABINOID SYSTEM

KW - MOTOR INCOORDINATION

KW - BRIEF ANOXIA

U2 - 10.1016/j.neuropharm.2006.12.003

DO - 10.1016/j.neuropharm.2006.12.003

M3 - Article

C2 - 17382973

SN - 0028-3908

VL - 52

SP - 1327

EP - 1335

JO - Neuropharmacology

JF - Neuropharmacology

IS - 6

ER -