Richard W. Olsen
Department of Molecular & Medical Pharmacology
Recent Publications
Structural models of ligand-gated ion channels: sites of action for anesthetics and ethanol.
Cysteine substitutions define etomidate binding and gating linkages in the α-M1 domain of γ-aminobutyric acid type A (GABAA) receptors.
Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders.
Ethanol promotes clathrin adaptor-mediated endocytosis via the intracellular domain of δ-containing GABAA receptors.
Dihydromyricetin as a novel anti-alcohol intoxication medication.
Olsen’s research has focused on the structure and function of GABAA receptors, including studies on the structural basis of receptor pharmacological heterogeneity, establishment of functional domains in the GABAA receptor protein, and intracellular trafficking of GABAA receptors into and out of synapses.

They have also established an animal model of alcohol dependence and epileptogenesis and an animal model of mental retardation and epilepsy. In the first case, ethanol is administered to rats on an intermittent chronic regimen which results in increased severity of withdrawal and a persistent kindled-like state of hyperexcitability, with increased anxiety and sleep disturbance. This is associated with hypoinhibition in the hippocampus, due to altered GABAA receptor subunit composition.

In the second case, mice lacking certain GABAA receptor subunits are studied to learn about their function in the brain. Animals lacking the beta 3 subunit have epilepsy and other neuropsychiatric abnormalities resembling the human genetic disease Angelman syndrome. Trainees participate in this research at the level of molecular biology (making gene targeting constructs, transfected embryonic stem cells, and transgenic mice), molecular pharmacology (studying recombinant GABA receptors in cell expression systems, using radioligand receptor binding and signal transduction assays, including electrophysiology, and studying brains in vitro from treated animals), and animal behavior (characterizing mutant and transgenic mice).