RESUMO
Recent studies show contradictory results regarding the contribution of endocannabinoids in fear memory formation and long-term synaptic plasticity. In this study, we investigated the effects of both cannabinoid receptor type 1 (CB1 receptor) antagonist AM281 and anandamide reuptake inhibitor AM404 on the formation of contextual fear memory in adult mice. Both i.p. and intra-hippocampal injections of AM281 promoted contextual fear memory while a high dose of AM404 inhibited it. These findings demonstrate that CB1 receptor-mediated signaling negatively contributes to contextual fear memory formation. We further investigated the induction of long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices and found that AM281 impaired the induction of LTP. Additionally, the blockade of LTP by AM281 was completely prevented by bath application of picrotoxin, a selective antagonist of GABA(A) receptor. Taken together, these results indicate that activation of CB1 receptor contributes to induction of LTP via a GABA(A) receptor-mediated mechanism.
Assuntos
Moduladores de Receptores de Canabinoides/fisiologia , Endocanabinoides , Medo/fisiologia , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Animais , Ácidos Araquidônicos/farmacologia , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Antagonistas GABAérgicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microinjeções , Morfolinas/farmacologia , Neurônios/efeitos dos fármacos , Picrotoxina/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacosRESUMO
The potential to exhibit synaptic plasticity itself is modulated by previous synaptic activity, which has been termed as metaplasticity. In this paper, we demonstrated that the activation of N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) subunit in NNDA receptors was required for hippocampal metaplasticity at Schaffer collateral-commissural fiber-CA1 synapses. Brief 5 Hz priming stimulation did not cause long-term synaptic plasticity; however, it could result in the inhibition of subsequently evoked long-term potentiation (LTP). Meanwhile, the application of selective antagonists for NR2B subunit of NMDA receptors after delivering priming stimulation could block the metaplasticity. In contrast, LTP induction was not affected by NR2B antagonists in slices without pre-treatment of priming stimulation. These results indicated that the activation of NR2B-containing NMDA receptors was required for metaplasticity.
