Antagonizing α7 nicotinic receptors with methyllycaconitine (MLA) potentiates receptor activity and memory acquisition

Add time:07/24/2019    Source:sciencedirect.com

α7 nicotinic acetylcholine receptors (α7nAChRs) have been targeted to improve cognition in different neurological and psychiatric disorders. Nevertheless, no α7nAChR activating ligand has been clinically approved. Here, we investigated the effects of antagonizing α7nAChRs using the selective antagonist methyllycaconitine (MLA) on receptor activity in vitro and cognitive functioning in vivo. Picomolar concentrations of MLA significantly potentiated receptor responses in electrophysiological experiments mimicking the in vivo situation. Furthermore, microdialysis studies showed that MLA administration substantially increased hippocampal glutamate efflux which is related to memory processes. Accordingly, pre-tetanus administration of low MLA concentrations produced longer lasting potentiation (long-term potentiation, LTP) in studies examining hippocampal plasticity. Moreover, low doses of MLA improved acquisition, but not consolidation memory processes in rats. While the focus to enhance cognition by modulating α7nAChRs lies on agonists and positive modulators, antagonists at low doses should provide a novel approach to improve cognition in neurological and psychiatric disorders.

We also recommend Trading Suppliers and Manufacturers of METHYLLYCACONITINE CITRATE (cas 112825-05-5). Pls Click Website Link as below: cas 112825-05-5 suppliers

Prev:Molecular heterogeneity of human motilinlike immunoreactivity explained by the processing of prepromotilin (cas 112820-96-9)
Next:Nicotine cue: lack of effect of the α7 nicotinic receptor antagonist methyllycaconitine)