INHIBITION OF LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES BY ANANDAMIDE AND WIN55212-2 - REVERSAL BY SR141716-A, A SELECTIVE ANTAGONIST OF CB1 CANNABINOID RECEPTORS

It has been reported previously that Delta(9)-tetrahydrocannabinol and the synthetic cannabinoid agonist HU-210 [(-)-11-OH-Delta(8)-dimethylheptyl tetrahydrocannabinol] prevent long-term potentiation (LTP) induction in rat hippocampal slices. In this study we confirm that both WIN55212-2 {R-(+)-(2,3-dihydro-5-methyl-3-[{4-morpholinyl}methyl]pyrol [1,2,3-de]-1,4-benzoxazin-6-yl) (1-naphtalenyl) methanone monomethanesulphonate} (3 and 10 mu M), another synthetic cannabinoid agonist, and anandamide (10 mu M), considered to be the endogenous ligand of cannabinoid receptors, inhibit LTP formation in the Schaffer collateral-CA1 field complex. In addition, we show that SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] at 0.1-10 mu M, a potent and selective antagonist of CB1 cannabinoid receptors, concentration-dependently reversed the inhibition of LTP induced by both WIN55212-2 and anandamide. These data indicate that cannabinoid receptor agonists inhibit hippocampal LTP formation through CB1 receptor activation and that anandamide could be a candidate for an endogenous neuromessenger involved in memory processes.