COX-2 modulates Δ~9-THC-induced inhibition of LTD in CA1 area / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the role of cyclooxgense-2 (COX-2) in tetrahydrocannabinol (THC)-induced inhibition of long-term depression (LTD) in CA1 area in vitro. Methods The hippocampal slices were prepared at 24 h after intraperitoneal injection of Δ~9-THC (10 mg/kg) or COX-2 inhibitor NS398 (10 mg/kg). Field excitatory post-synaptic potentials (fEPSP) were recorded in the stratum radiatum of the CA1 area in vitro to observe the effect of NS398, a selective inhibitor of COX-2, on the THC-induced inhibition of LTD and THC's effect on membrane excitability in pyramidal neurons by using the whole-cell patch clamp technique. Results ① Low-frequency stimulation (1 Hz, 15 min) induced-LTD in CA1 area was significantly attenuated by Δ9-THC. ② Δ~9-THC did not affect the basal synaptic transmission and membrane excitability (including membrane resting potentials, input resistance and firing property). ③ THC-induced inhibition of LTD was reversed by NS398. ④ THC-induced inhibition of LTD was robustly impaired in COX-2 knockout mice. Conclusion THC-induced inhibition of LTD in CA1 area was mediated via COX-2.