Paeoniflorin, a major constituent of peony root, reverses muscarinic M1-receptor antagonist-induced suppression of long-term potentiation in the rat hippocampal slice

We previously reported that paeoniflorin but not albiflorin, components of peony root, produced ameliorative effects on scopolamine-induced spatial cognitive impairment in rats. In this study, we examined the effects of paeoniflorin and muscarinic receptor antagonists on long-term potentiation (LTP) of population spike recorded from the CA1 region of rat hippocampal slices. Bath applications of an M-1- and M-2-receptor antagonist scopolamine and a selective M-1-receptor antagonist pirenzepine, at a concentration of 10 mu M, significantly suppressed LTP, whereas AF-DX116, a selective M-2-receptor antagonist, failed to affect it. Paeoniflorin (0.1-1 mu M), which alone was ineffective on LTP induction, significantly reversed the suppressive effects of scopolamine and pirenzepine (10 mu M). In contrast, albiflorin (0.1-1 mu M) had no effect on the scopolamine-induced LTP suppression. These results suggest that paeoniflorin reversal of the muscarinic M-1-receptor-mediated inhibition of LTP may be implicated in the ameliorative effect of paeoniflorin on spatial cognitive impairment caused by cholinergic dysfunction.