Inhibition by anandamide and synthetic cannabimimetics of the release of [3H]D-aspartate and [3H]GABA from synaptosomes isolated from the rat hippocampus.
Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K(+)-evoked release of [3H]D-aspartate ([3H]D-ASP) and [3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [3H]D-ASP and [3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2'-chloroethylamide/N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), as well as by the endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG). Both types of release were also inhibited by capsaicin. The inhibition produced by each of the cannabinoid compounds and capsaicin was unaffected by capsazepine or by the CB1-receptor antagonists AM-251 and SR141716A. The mechanism underlying AEA- and synthetic CB-induced inhibition of the release of [3H]GABA and [3H]D-ASP from rat hippocampal synaptosomes might not involve activation of presynaptic CB1 receptors.
D'Amico
M
M
Institute of Pharmacology, Catholic University of S. Heart, Rome, Italy.
Cannizzaro
C
C
Preziosi
P
P
Martire
M
M
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D063388:Endocannabinoids; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D011188:Potassium; D002211:Capsaicin; D002118:Calcium; C078814:anandamide