在体研究Anandamide和Win55,212-2对海马CA1区长时程增强的不同作用

annabinoids are believed to alter cognition and prevent long-term potentiation (LTP) via cannabinoid receptor (CB1) activation, but the effects of endogenous and synthetic cannabinoids seem not always identical. Here, we compared the effects of endogenous cannabinoids anandamide (AEA) and synthetic counterparts WIN 55,212-2 (WIN) on synaptic plasticity in hippocampal CA1 region of the anesthetized rats. CB1 blockade by AM281 attenuated high frequency stimulation (HFS)-LTP significantly, but ANA in the micromolar range (1~100μM) also inhibited LTP, whereas ANA with lower concentration (0.1μM) exhibited significant enhancement of LTP. It seemed ANA exerted dual actions on LTP induction. However, WIN potently attenuated basal synaptic transmission and HFS-LTP dose-dependently. Furthermore, the decrease of LTP induced by ANA, but not WIN, could be restored to control level after forskolin application, suggesting the inhibitory potency of ANA on adenylyl cyclase is weaker than WIN. In conclusion, our results reveal some differential effects of endogenous and synthetic cannabinoids in vivo and suggest AEA probably play a more subtle physiological role in the hippocampus than the solely prevention of LTP.