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Cannabinoids inhibit the release of [ 3 H]glutamate from rodent hippocampal synaptosomes via a novel CB 1 receptor‐independent action
Author(s) -
Köfalvi Attila,
Vizi E. Sylvester,
Ledent Catherine,
Sperlágh Beáta
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02897.x
Subject(s) - glutamate receptor , am251 , cannabinoid , agonist , chemistry , pharmacology , cannabinoid receptor , nmda receptor , hippocampal formation , receptor , biochemistry , biology , neuroscience
In this study we investigated the effect of cannabinoids on [ 3 H]glutamate release from hippocampal synaptosomes of rat and CB 1 ‐null mutant mouse. In the rat, cannabinoid receptor agonists, i.e. CP55,940 (EC 50 , 0.84 μ m ), WIN55,212‐2 (EC 50 , 3.47 μ m ), ACEA (EC 50 , 17.8 μ m ), and R‐(+)‐methanandamide (EC 50 , 19.8 μ m ) concentration‐dependently inhibited the 25‐m m ‐K + depolarization‐evoked release of [ 3 H]glutamate and, among them, WIN55,212‐2 displayed the greatest efficacy. The CB 1 receptor antagonists SR141716A (1–5 μ m ) and AM251 (1 μ m ) and the VR 1 vanilloid receptor antagonist capsazepine (10 μ m ) did not antagonize the effect of the agonists. SR141716A by itself attenuated the evoked [ 3 H]glutamate release. WIN55,212‐2 inhibited the release of [ 3 H]glutamate in \mathrm{CB}^{\,‐/‐\,}_{1} mice as well. These data demonstrate that the action of cannabinoids on glutamate release in the hippocampus is pharmacologically distinct and independent from the cloned CB 1 receptor.