WINSTON-SALEM, N.C. – Depressed monkeys not only look and act like depressed people, but their central nervous systems have the same characteristics, a finding that could lead to more effective testing of depression treatments.
“Brain scans of depressed female monkeys revealed the same underlying neurobiological changes that are found in the brains of depressed people,” said Carol A. Shively, Ph.D., from Wake Forest University School of Medicine. “This is further evidence that these animal models can help researchers understand depression, develop new treatments and test their effectiveness.” This study is reported in the April issue of the Archives of General Psychiatry.
The brain scans looked at a specific type of receptor (called the 5-HT1a receptor) that binds serotonin, a brain chemical that controls mood. Serotonin binding is lower in depressed people.
Positron emission tomography (PET), a test that produces three-dimensional views of the brain, was used to scan 11 areas of the brain. A tracer that binds to this serotonin receptor was injected into a vein of each subject.
The areas in which the tracer binds in the brain light up bright yellow during the PET scan. The depressed monkeys had lower serotonin receptor binding in all areas of the brain examined, just like previous studies have shown in depressed people.
This supports earlier studies showing that depressed female monkeys have similar physical characteristics to women who are depressed, including low activity levels, disruptions in hormones and higher heart rates.
“Even though women are twice as likely as men to experience clinical depression and are at increased risk for depression during premenstrual, postpartum and perimenopausal times in their lives, we have never had any female animal models of depression,” said Shively, a professor of comparative medicine. “Monkeys offer a special opportunity for research because they are among the few animals that have menstrual cycles and complex cognitive function.”
In addition, these animals have “pure” systems when it comes to medicine. They have no experience with selective serotonin reuptake inhibitor (SSRI) drugs such as Paxil, Prozac and Zoloft, that are often used to treat depression and can alter neurotransmissions, nor have they taken analgesics, alcohol, tobacco or illegal drugs, Shively said.
Monkey models can be used to develop new treatments and test their effectiveness, Shively said, through observing their behavior and using brain scans to reveal if treatments or medications are actually working.
“Another way we’d like to see the model used is to investigate the cognitive aspects of depression,” Shively said. “The way that many of our pharmaceutical products got onto the market was that they were tested on rodents. But when they were used by humans, we found side effects that caused cognitive dysfunction like lack of concentration. Depressed people do not need more cognitive dysfunction. This animal model could be used to test treatments that alleviate cognitive problems associated with depression rather than making them worse.”
Shively pointed out that there are very few places in the country that have both a primate center and an imaging center that made this study possible. “This research cannot be done without having both centers here.”
Other Wake Forest Baptist researchers participating in the study were David P. Friedman, Ph.D., Physiology and Pharmacology; H. Donald Gage Jr., Ph.D., Michael C. Bounds, B.A., Clive Brown-Proctor, Ph.D., Joseph B. Blair, Ph.D., and Nancy C. Buchheimer, B.S., all from Radiology; and Jessica A. Henderson, Ph.D., and Michael A. Smith, M.S., both graduate students in the Integrative Neuroscience Program.
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Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 30th in primary care, 41st in research and 14th in geriatrics training among the nation's medical schools. It ranks 32nd in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.