Underlying mechanisms of long-term potentiation during the inhibition of the cannabinoid CB1 and GABAB receptors in the dentate gyrus of hippocampus

Background and Aim : It is important to determine the pre- and/or postsynaptic locus of Long-term potentiation (LTP) expression in order to study its underlying mechanisms. The aim of the present study was to investigate whether LTP induction acutely induced by cannabinoid CB1 and GABAB receptors antagonists occurs at the presynaptic or postsynaptic sites, or at both.Methods : Male Wistar rats were randomly divided into following groups: Control (90% saline + 10% DMSO,), AM251, CGP55845, CGP55845 + AM251. After cannulation, AM251 and CGP55845 were microinjected into dentate gyrus (DG) of hippocampus, as antagonists of CB1 and GABAB receptors, respectively. LTP in the hippocampal area was induced by high-frequency stimulation (HFS) of the perforant path (PP). The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in DG area of adult rats in response to stimulation applied to the PP. The paired-pulse ratio (PPR) was measured before and after the induction of LTP in all groups.Results : Statistical analysis using Two-Way ANOVA followed by Sidak’s test for multiple comparison revealed that AM-251 produced significant increase in slope of EPSP and amplitude of PS (p < 0.01). Conversely, administration of CGP55845 produced decrease in slope of EPSP (p < 0.01). We observed that PPR was not affected by LTP induction in the presence of AM251 or CGP55845 either alone or their combination (p > 0.05).Conclusion : Based on our results the site responsible for LTP expression is, at least partly, the postsynaptic site, because PPR is widely considered to be of presynaptic origin. It seems that contribution of CB1 and GABAB receptors to LTP have centered on NMDA receptor-dependent form of LTP because we observed that PPR was not affected by LTP induction in the presence of AM251 or CGP55845 either alone or their combination.

کلیدواژه ها:

Hippocampus ، Paired-Pulse Ratio ، Cannabinoid CB1 receptors ، GABAB receptors ، Long Term Potentiation