Work

GABA A Receptor Subtypes: Therapeutic Potential in Down Syndrome, Affective Disorders, Schizophrenia, and Autism

Year: 2013

Type: review

Abstract: The γ-aminobutyric acid (GABA) system plays a pivotal role in orchestrating the synchronicity of local networks and the functional coupling of different brain regions. Here we review the impact of the GABAA receptor subtypes on cognitive and emotional behavior, paying particular attention to five disease states: cognitive dysfunction and Down syndrome, anxiety disorders, depression, schizophrenia, and autism. Through the bidirectional modulation of tonic inhibition, α5-subunit-containing GABAA receptors permit the bidirectional modulation of cognitive processes, and a partial inverse agonist acting at the α5-subunit-containing GABAA receptor is in a clinical trial in individuals with Down syndrome. With regard to anxiety disorders, the viability of nonsedative anxiolytics based on the modulation of α2- and α3-subunit-containing GABAA receptors has been established in clinical proof-of-concept trials. Regarding the remaining three disease states, the GABA hypothesis of depression offers new options for antidepressant drug development; cognitive symptoms in schizophrenia are attributed to a cortical GABAergic deficit, and dysfunctional GABAergic inhibition is increasingly understood to contribute to the pathophysiology of autism spectrum disorders.

Source: The Annual Review of Pharmacology and Toxicology

DOI: 10.1146/annurev-pharmtox-011613-135947

Authors: Uwe Rudolph, Hanns Möhler

Institutions: Harvard University, McLean Hospital, University of Zurich, ETH Zurich

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences