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The GABAA agonist muscimol encapsulated in liposomes as a tool for the chronic inhibition of the central nervous system
Author(s) -
Silva Luiz Gonzaga,
Oliveira Aline Cristina,
Santos Robson Augusto,
Frezard Frederic,
Fontes Marco Antonio
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1065.24
Subject(s) - muscimol , microinjection , liposome , agonist , gabaa receptor , pharmacology , chemistry , medicine , anesthesia , endocrinology , receptor , biochemistry
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