New research shows that a unique strain of laboratory mice characterized at Penn State University has behavioral, hormonal, and neurochemical characteristics that are similar to those of human patients with drug-resistant forms of depression. The mice -- which have a defect in a gene -- are expected to be useful as a new model organism in the effort to develop more effective medications for specific forms of depression. The research, led by Bernhard Luscher, a professor of biology at Penn State, will be published in the journal Biological Psychiatry.
"A mouse can't tell us if it is feeling depressed, so we used a number of different kinds of tests -- including some new ones that we developed -- to gauge behavioral and hormonal changes, or phenotypes, of a type of depression that, in humans, does not respond well to some antidepressant drugs," Luscher said. "These indicators include reduced exploration of novel or otherwise aversive environments, failure to escape from a highly stressful situation, and reduced pleasure-seeking behavior such as a reduced preference for sweet over plain water."
The genetic defect in the depressed mice interferes with the function of a protein in the brain called the GABA-A receptor, which controls the response to the neurotransmitter gamma-aminobutryic acid. Reduced function of these receptors has been known to be be involved in anxiety disorders -- but not in depression -- because currently available drugs that activate the GABA-A receptor are ineffective as antidepressants. "We have shown in this paper that this long-held conviction is flawed," Luscher said. "Our research shows that the GABA-A receptor is, in fact, an important part of the brain circuitry that is not working properly in depression."
The genetically defective, GABA-A-receptor-deficient mice in Luscher's lab previously had been shown to be a good model organism for studies of anxiety, which often occurs along with depr
|Contact: Barbara K. Kennedy|