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

Naunyn Schmiedebergs Arch Pharmacol. 1995 Nov;352(5):576-9. doi: 10.1007/BF00169393.


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 microM), another synthetic cannabinoid agonist, and anandamide (10 microM), 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 microM, 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.

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology*
  • Benzoxazines
  • Cannabinoids / metabolism
  • Endocannabinoids
  • Evoked Potentials / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Morpholines / pharmacology*
  • Naloxone / administration & dosage
  • Naphthalenes / pharmacology*
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors*
  • Receptors, Drug / metabolism
  • Rimonabant


  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoids
  • Endocannabinoids
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Naloxone
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant
  • anandamide