Neurological Roots of Depression

Stressed rats used to study human depression

Published in The California Aggie (theaggie.org) on March 9, 2011

Story and Photo by Hudson Lofchie

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With the stress of academics and the paltry job market, no one can blame college students for feeling a little down. Psychologists know that these stresses can snowball into full-blown depression. At UC San Diego, scientists are experimenting with a new tool for studying depression: rats.

A recent study on rat brains at UC San Diego has shown that depression is triggered by the activation of a part of the brain called the lateral habenula (LHb). The researchers from UCSD, Cold Spring Harbor Laboratory and Brookhaven National Laboratory are searching for ways to control this activation to more effectively treat depression.

“[The LHb] becomes active when an animal fails to receive an expected reward,” said Roberto Malinow, a professor of neurosciences at the UCSD School of Medicine. “It is also active when an animal receives a signal indicating a negative outcome.”

The LHb is also connected to other regions of the brain that control reward response, the sleep/wake cycle and eating. Since the LHb is connected to all these systems, depression can lead to sleep disorders, compulsive behavior and eating disorders.

The researchers performed tests on two types of rats. One test group of rats was intentionally bred for congenital learned helplessness, a genetic predisposition to depression. The other test group of rats was originally normal, but then put through stressful situations to trigger a condition called acute learned helplessness.

“We used two behavioral measurements: one is the force swim test, the other is the learned helplessness test,” said Bo Li, a researcher at Cold Spring Harbor Laboratory.

The “learned helplessness test” tested how hard a rat would try to escape an unpleasant situation. According to Malinow, animals that model a depressed state have a high threshold to avoid unpleasant stimuli, which means they lack the motivation to seek a better environment.

The researchers measured the neural activity in the rats with a method called whole-cell patch clamp recording, a process where the brain is removed from the rats, and then cut into thin slices. The brain cells can be maintained alive for about eight hours once removed from the body.

“We use glass pipettes that are 1 micron thin that can be used to measure electrical activity in the neurons,” said Malinow.

Testing rats with congenital learned helplessness could give insight into how depression is triggered in humans. Depression is a condition that a person can be genetically predisposed to, but that does not necessarily mean that depression is guaranteed by genes.

“In many cases, an interaction between [genetically] inherited factors and environmental factors determine whether we become depressed or not,” said Dorje Jennette, a psychologist for Counseling and Psychological Services.

Aside from genetic predisposition, environmental factors for stress include abusive childhoods, chronic illnesses or pain, unemployment and low self-esteem.

“UC Davis is a competitive university, and with that competitiveness comes significant stress levels,” said Jennette. “On top of that, UC students [are] facing financial stressors on multiple fronts, such as at home, at school and in the job market.”

Some of the signs of depression are difficulty focusing, lack of motivation and apathy.

“At the extreme, feelings of apathy involve not caring enough to get out of bed to go to class, or even to social gatherings that previously would have been considered fun,” Jennette said.

The more stressful college becomes, the more important it is to have easy access to needed help. This includes services like CAPS, as well as friends who are willing to help.

According to Jennette, supportive friends go a long way toward Gandhi’s suggestion that you “be the change you want to see in the world.”

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