Many structurally different classes of compounds with central nervous system (CNS) depressant effects, such as the barbiturates, general anesthetics, neurosteroids, alcohol, and the benzodiazepines, modulate synaptic inhibition mediated by the GABAA receptor (GABAA-R) in the mammalian CNS. In many cases, this is likely to be the primary mechanism by which these drugs induce acute intoxication, provide clinically useful therapy, exert side effects, and/or mediate abuse liability. The molecular nature of the interaction of these agents with the GABAA-R is not well understood and, with the exception of the benzodiazepines, the sites of binding have not been characterized. The goals of the proposed research are to study the pharmacology and electrophysiology of chimeric receptors containing portions of human GABAA-R subunits together with complementary pieces of the related glycine receptors or the GABA rho subunits (the 'GABAc receptor'). In particular, the proposed research will focus on the barbiturates. These chimeras were chosen to combine homologous ligand- gated receptor subunits that are modulated by barbiturates (e.g., GABA-Rs) with those that are insensitive to barbiturate modulation (e.g., the rho1 subunit) to gain information about the molecular nature of the sites of interaction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH011504-03
Application #
2674540
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Program Officer
Goldschmidts, Walter L
Project Start
1998-07-10
Project End
Budget Start
1998-07-10
Budget End
1999-07-09
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637