Learned safety cheers depressed mice: An animal model of behavioral intervention for depression

October 08, 2008

A new animal model has provided insight into the cellular and molecular mechanisms associated with behavioral therapy for depression. The study, published by Cell Press in the October 9th issue of Neuron, may provide a good model system for testing cellular and molecular interactions between antidepressive medications and behavioral treatments for depression.

Organisms ranging from simple invertebrates to mammals have evolved mechanisms for instinctive and learned fear that are critical for survival. However, in humans, pathological forms of learned fear can contribute to anxiety disorders, posttraumatic stress, and depression. "The fact that learned fear can be associated with psychopathologies in humans suggests that this form of learning is not always appropriate and that effective inhibitory constraints are likely to exist," explains Eric Kandel from Columbia University.

Previous research investigating how learned fear is processed in the brain has made use of a conditioned inhibition learning paradigm wherein an animal is conditioned to associate a target signal with protection from an impending aversive event, resulting in a reduction of conditioned fear. This process, where an animal learns to take advantage of sources of security in the environment, is thought to represent a form of "learned safety."

Daniela Pollak in the Kandel lab was interested in attempting to characterize some of the behavioral consequences of learned safety as well as exploring the phenomenon at the molecular level. She observed that learned safety reduced depression-like behavior in mice in a manner that was comparable to that seen with pharmacological antidepressants. Consistent with the behavioral antidepressant effects, learned safety also shared neurobiological hallmarks associated with other antidepressant therapies. Specifically, learned safety promotes the survival of newborn nerve cells and expression of critical growth factors in the hippocampus.

The researchers went on to search for differentially regulated genes in the amygdala of safety- and fear-conditioned mice. The amygdala is a brain region associated with emotional symptoms that are a hallmark of depression. Learned safety led to decreased expression of genes involved in dopamine and substance P signaling, but not serotonin signaling. This is significant because serotonin receptors are a major target of popular antidepressant medications.

"We propose a model in which the stress-reducing and antidepressant effects of learned safety are mediated through the interaction of (at least) two different neurotransmitter systems. Our findings suggest that learned safety is an animal model of a behavioral antidepressant that shares some of the neuronal modifications typical of pharmacological antidepressant, but is mediated by different molecular pathways," offers Kandel.
-end-
The researchers include Daniela D. Pollak, Columbia University, New York, NY; Francisco J. Monje, Columbia University, New York, NY; Lee Zuckerman, Columbia University, New York, NY; Christine A. Denny, Columbia University, New York, NY; Michael R. Drew, Columbia University, New York, NY; and Eric R. Kandel, Columbia University, New York, NY and Howard Hughes Medical Institute.

Cell Press

Related Depression Articles from Brightsurf:

Children with social anxiety, maternal history of depression more likely to develop depression
Although researchers have known for decades that depression runs in families, new research from Binghamton University, State University of New York, suggests that children suffering from social anxiety may be at particular risk for depression in the future.

Depression and use of marijuana among US adults
This study examined the association of depression with cannabis use among US adults and the trends for this association from 2005 to 2016.

Maternal depression increases odds of depression in offspring, study shows
Depression in mothers during and after pregnancy increased the odds of depression in offspring during adolescence and adulthood by 70%.

Targeting depression: Researchers ID symptom-specific targets for treatment of depression
For the first time, physician-scientists at Beth Israel Deaconess Medical Center have identified two clusters of depressive symptoms that responded to two distinct neuroanatomical treatment targets in patients who underwent transcranial magnetic brain stimulation (TMS) for treatment of depression.

A biological mechanism for depression
Researchers report that in depressed individuals there are increased amounts of an unmodified structural protein, called tubulin, in lipid rafts compared with non-depressed individuals.

Depression in adults who are overweight or obese
In an analysis of primary care records of 519,513 UK adults who were overweight or obese between 2000-2016 and followed up until 2019, the incidence of new cases of depression was 92 per 10,000 people per year.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.

Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.

CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.

Read More: Depression News and Depression Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.