Abstract:
:GABAA receptors mediate most of the fast inhibitory transmissions in the central nervous system. These receptors are pentameric complexes that exhibit high structural and pharmacological heterogeneity, as they can be constructed from 19 distinct subunits. GABAA receptors are the targets of numerous clinically relevant drugs used to treat various disorders such as anxiety, insomnia and epilepsy. These receptors are also the targets of many volatile anesthetics and drugs of abuse, such as alcohol. This review is focused on the effect of long-term treatment with GABA, and the positive allosteric modulators benzodiazepines, neurosteroids and ethanol on GABAA receptors. Prolonged exposure of GABAA receptors to these compounds triggers several adaptive mechanisms that lead to changes in the structure, function and localization of receptors. These changes include GABAA receptor subunit expression, intracellular trafficking and phosphorylation. These adaptations are relevant to different physiological, pathological and pharmacological conditions and, in most cases, are associated with the development of tolerance. Understanding the molecular mechanisms underlying these regulatory processes will be relevant for therapeutic benefits.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Gravielle MCdoi
10.1016/j.neuint.2018.05.015subject
Has Abstractpub_date
2018-09-01 00:00:00pages
96-104eissn
0197-0186issn
1872-9754pii
S0197-0186(18)30021-4journal_volume
118pub_type
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