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Interactions of cannabidiol with endocannabinoid signalling in hippocampal tissue
Author(s) -
Ryan Duncan,
Drysdale Alison J.,
Pertwee Roger G.,
Platt Bettina
Publication year - 2007
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 - 10.1111/j.1460-9568.2007.05448.x
Subject(s) - endocannabinoid system , anandamide , cannabinoid receptor , cannabidiol , 2 arachidonoylglycerol , cannabinoid , palmitoylethanolamide , chemistry , depolarization induced suppression of inhibition , pharmacology , hippocampal formation , neuroscience , microbiology and biotechnology , biology , receptor , antagonist , biochemistry , medicine , cannabis , psychiatry
The phytocannabinoid cannabidiol (CBD) possesses no psychotropic activity amid potentially beneficial therapeutic applications. We here characterized interactions between CBD (1 µ m ) and the endocannabinoid system in cultured rat hippocampal cells. The CBD‐induced Ca 2+ rise observed in neurons and glia was markedly reduced in the presence of the endogenous cannabinoid anandamide in neurons, with no alteration seen in glia. Neuronal CBD responses were even more reduced in the presence of the more abundant endocannabinoid 2‐arachidonyl glycerol, this action was maintained in the presence of the CB 1 receptor antagonist AM281 (100 n m ). Neuronal CBD responses were also reduced by pre‐exposure to glutamate, expected to increase endocannabinoid levels by increasing in [Ca 2+ ] i . Application of AM281 at 1 µ m elevated CBD‐induced Ca 2+ responses in both cell types, further confirming our finding that endocannabinoid‐mediated signalling is negatively coupled to the action of CBD. However, upregulation of endogenous levels of endocannabinoids via inhibition of endocannabinoid hydrolysis (with URB597 and MAFP) could not be achieved under resting conditions. Because Δ 9 ‐tetrahydrocannabinol did not mimic the endocannabinoid actions, and pertussis toxin treatment had no effect on CBD responses, we propose that the effects of AM281 were mediated via a constitutively active signalling pathway independent of CB 1 signalling. Instead, signalling via G q/11 and phospholipase C appears to be negatively coupled to CBD‐induced Ca 2+ responses, as the inhibitor U73122 enhanced CBD responses. Our data highlight the interaction between exogenous and endogenous cannabinoid signalling, and provide evidence for the presence of an additional pharmacological target, sensitive to endocannabinoids and to AM281.