Alberta Innovates- Health Solutions

Dr. Alan Bateson studies how the GABA_A receptor, which acts like a gate to nerve cells in the brain, works. The key to this gate is GABA, a chemical messenger that lets nerve cells talk to each other. When the GABA key opens the GABA_A receptor gate, chloride ions slip through, inhibiting the signals that fire up the cell.

Dr. Bateson aims to discover how the brain controls the GABA_A receptor genes and how long-term drug use changes them. "We've isolated one of the genes that produces the GABA_A receptor and discovered regions of the gene involved in controlling GABA_A's expression," he explains.

GABA_A is the target for benzodiazepines such as Valium and Librium, drugs commonly prescribed for anxiety and sleep disorders.

When patients take Valium or its related drugs for a long time (normally two to three weeks), two things can happen. They can become tolerant to the effects of the drugs, or they can experience unpleasant side effects if they stop taking them.

Dr. Bateson has discovered that long-term benzodiazepine use changes GABA_A receptors, making them less sensitive to the drug. When the drugs are abruptly stopped, the wrong receptor for that particular neuronal network is expressed, so the neurons have to adapt back again. "It takes a while for the brain to adjust to the change. We believe that's what causes withdrawal symptoms."

Understanding how the original receptor tells the genes in the cell's nucleus to express different receptors could provide a new approach to treating disorders such as sleeplessness and anxiety, the Heritage researcher says. "If we can understand the process, maybe we can design new drugs, acting possibly by the same mechanisms, that can get around problems such as tolerance and withdrawal."

Dr. Alan Bateson is a Heritage Scholar and Associate Professor in the Department of Pharmacology in the Faculty of Medicine and Dentistry at the University of Alberta. In addition to Heritage funding, Dr. Bateson receives support from the Medical Research Council of Canada.
Several Heritage students and post-docs have worked in Dr. Bateson's lab including

• Robert Holt
• Glen Newell
• Dr. Michelle Arnot
• Dr. Chien-Tsai Lai
• Dr. Catherine Ten
• Dr. Veronique Tanay