A Selective M1 and M3 Receptor Antagonist, Penehyclidine Hydrochloride, Exerts Antidepressant-Like Effect in Mice.

A Selective M1 and M3 Receptor Antagonist, Penehyclidine Hydrochloride, Exerts Antidepressant-Like Effect in Mice. Neurochem Res. 2019 Oct 12;: Authors: Sun X, Sun C, Zhai L, Dong W Abstract Recent studies indicate that anti-muscarinic receptor is a prospective strategy to treat depression. Although non-selective antagonist of muscarinic receptor scopolamine exhibits rapid and robust antidepressant-like effect, it still has various side effects including abuse risk. Penehyclidine hydrochloride (PHC) is a novel clinical anti-cholinergic drug derived from scopolamine in China, which selectively blocks M1 and M3 muscarinic receptor. Therefore, the objective of this study was to evaluate whether PHC would manifest antidepressant-like effects. Forced swim test (FST), tail suspension test (TST) and chronic unpredictable mild stress (CUMS) model of depression were explored to assess the antidepressant-like effect. Western blotting was further performed to detect the effects of PHC on the brain-derived neurotrophic factor (BDNF) signal cascade. Immunofluorescence was used to observe the activation of astrocyte. Moreover, different pharmacological inhibitors were applied to clarify the antidepressant-like mechanism. The results of the present experiments revealed that PHC decreased the immobility time of FST and TST in mice. In the CUMS model, PHC rapidly ameliorated anhedonia-like behavior (within 4 days), accompanying with the enhanced ex...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research