A comparison of the activity of the animals' brain cells in normal and stressed rats revealed that stress had no effect on the levels of serotonin in the 'depressed' brains. Instead, it was the excitatory connections that responded to serotonin in strikingly different manner. These changes could be reversed by treating the stressed animals with antidepressants until their normal behavior was restored.
"In the depressed brain, serotonin appears to be trying hard to amplify that cocktail party conversation, but the message still doesn't get through," says Dr. Thompson. Using specially engineered mice created by collaborators at Johns Hopkins University School of Medicine, the study also revealed that the ability of serotonin to strengthen excitatory connections was required for drugs like antidepressants to work.
Sustained enhancement of communication between brain cells is considered one of the major processes underlying memory and learning. The team's observations that excitatory brain cell function is altered in models of depression could explain why people with depression often have difficulty concentrating, remembering details, or making decisions. Additionally, the findings suggest that the search for new and better antidepressant compounds should be shifted from drugs that elevate serotonin to drugs that strengthen excitatory connections.
"Although more work is needed, we believe that a malfunction of excitatory connections is fundamental to the origins of depression and that restoring normal communication in the brain, something that serotonin apparently does in successfully treated patients, is critical to relieving the symptoms of this devastating disease," Dr. Thompson explains.
|Contact: Karen Robinson|
University of Maryland Medical Center