The GABAA agonist muscimol encapsulated in liposomes as a tool for the chronic inhibition of the central nervous system

Post by **Amanita Research** » Sat Oct 05, 2019 9:02 pm

https://www.fasebj.org/doi/abs/10.1096/ ... nt.1065.24

Abstract: The GABAA agonist muscimol is widely used as inhibitor of central nervous system (CNS). Although the effects of muscimol microinjections are well known, there is a lack of information regarding the long-term effects of the inhibition of regions in the CNS. Liposomes are a potential tool for sustained release of short half-life compounds. The aim of this study was to encapsulate the GABAA agonist muscimol into liposomes and evaluate the effect of chronic release of muscimol into the DMH on the inhibition of stress-induced cardiovascular changes. Liposomes with encapsulated muscimol were prepared by the dehydration-rehydration method. The lipids used were DSPC, cholesterol and PEG2000-DSPE. Liposomes were injected into the DMH and rats were submitted to the air stress paradigm after 15, 180 and 420 minutes after microinjection. Empty liposomes and free muscimol were used as control. Microinjection of liposome-entrapped muscimol was found to inhibit the tachycardia induced by air stress paradigm and this inhibition lasted for at least 420 minutes after microinjection (79, 92 and 71% of tachycardia inhibition after microinjection at 15, 180 and 420 minutes respectively). Free muscimol inhibited the air stress-induced cardiovascular changes for only 15 minutes after microinjection. Empty liposomes were not able to block the tachycardia induced by the air stress paradigm. Muscimol-containing liposomes produced a long-term attenuation in the cardiovascular response to emotional stress in rats. This technique will emerge as a potential tool for the chronic intervention on the central nervous system with the neurotransmission mediated by GABA and its agonists. Support: Fapemig/CNPq

Notes: Muscimol lowers tachycardia in stressed rats when given in a time release form. Also attenuates response of heart to emotional events (Emotional stress?).