Potentiation of the action of anandamide on hippocampal slices by the fatty acid amide hydrolase inhibitor, palmitylsulphonyl fluoride (AM 374)

The electrically-evoked release of [H-3]acetylcholine from hippocampal brai n slices is inhibited by cannabinoid receptor agonists. The effect of palmi tylsulphonyl fluoride (AM 374), a recently developed inhibitor of fatty aci d amide hydrolase, in influencing the potency of exogenously added anandami de in this preparation was examined. Anandamide alone had relatively Little effect on [H-3]acetylcholine release. By contrast, in the presence of AM 3 74 (0.1 mu M), anandamide produced a significant inhibition of [H-3]acetylc holine release at all concentrations tested (0.1-10 mu M). In addition to e xperiments with AM 374 the effects of N-(4-hydroxyphenyl)arachidonamide (AM 404), a putative anandamide uptake inhibitor, was also examined. However, AM 404 at concentrations up to 10 mu M, was not found to significantly enha nce the effect of anandamide on electrically-evoked [H-3]acetylcholine rele ase. These results indicate that AM 374 potently inhibits endogenous amidas e activity and thus facilitates access of exogenous anandamide to cannabino id receptors in the hippocampal tissue. (C) 1999 Elsevier Science B.V. All rights reserved.