Patients who don't respond to Prozac have increased serum levels of the hormone cortisol, which in mice is called corticosterone. "Our mice also showed abnormal corticosterone levels analogous to those patients who don't respond to Prozac," Luscher said. "In people, the cortisol level is corrected by drugs such as desipramine, and so it is in our mice. Desipramine corrects corticosterone levels in our mice but fluoxetine does not."
Luscher's paper also describes how he has begun to use this mouse model of drug-resistant depression to learn about the role of developmental factors in the onset of depression. His research suggests that the hormonal defect alone is not sufficient to produce the behavioral symptoms of depression, at least not if the hormonal abnormality is present only in adulthood. "Some research indicates that if you are born with certain types of risk factors, and something highly stressful happens in your life, such as a war experience -- then that event can trigger a mood disorder if you already have a risk factor," Luscher said.
"One of the many things we now want to explore is whether a slightly different strain of GABA-A-receptor-deficient mice, which are behaviorally normal but have increased levels of stress hormones, are at risk of developing depression if they experience additional excessive stress," Luscher said. "We also want to understand in greater detail what happens in these mice biochemically -- to understand which genes throughout the entire genom
|Contact: Barbara K. Kennedy|