Stress-related Disorders

Most people experience stress occasionally or frequently as a part of our daily routine, perhaps in form of an overbearing workload or as a personal conflict. Although we know that chronic stress can be harmful to our health, contributing to psychiatric, cardiovascular and many other diseases, it is difficult to avoid or almost impossible to ignore. This is because stressors activate an ancient neuroendocrine system that serves to ready us to deal with a perceived or real danger.
Research in our institute investigates three different aspects of the stress-response system:

1. The role of the endogenous opioid system in the coordination of stress responses.

The endogenous opioid system is composed of neuropeptides, the endogenous opioids enkephalin, endorphin, dynorphin and nociceptin that activate g-protein coupled mu-, delta-, kappa-, or ORL1 opioid receptors. Opium, or its active ingredient morphine, after which the system is named, is a specific ligand of mu-receptors. With the use of pharmacological tools and gene knockout mice, we and others have shown that endogenous opioid peptides are important modulators of stress responses. Thus, they affect pain sensation, anxiety, aggression and the release of stress hormones after exposure to a variety of stressors.

Our current research projects aim to determine how endogenous opioid peptides influence the formation and extinction of stress-associated memories.

2. Stress and drug addiction

Stress has profound affects on drug taking and drug seeking behavior. It increases the consumption of many drugs of abuse (e.g. alcohol and nicotine), and it is able to increase craving for drugs in abstinent animals and humans. Thus, stress is an important factor contributing to the relapse of drug dependence. We are using mouse genetics to identify genes involved in stress responses and the re-instatement of drug seeking behaviors using specific crosses of relatively stress-prone and stress-resistant mouse lines. These studies have revealed a number of quantitative trait loci (QTL) that modulate these behavioral responses. We are also using mouse line with specific gene deletions to analyze the involvement of selected candidate gene.

3. Chronic stress and depression

Chronic stress is one important factor contributing to the development of affective disorders. Indeed, chronic exposure to stressors is a commonly used method to elicit depression-like behavioral symptoms in animal models. The procedures used vary substantially and may include the repeated exposure to a dominant conspecies animal, or the presentation of random mild stressors over an extended period of time. We have recently established a novel method whereby depressive symptoms were induced by exposing nocturnal mice to a prolonged light period of 22 hours. With the use of these methods we aim to determine the molecular changes associated with depressive symptoms in limbic system structures and to assess the role of specific neuromodulators systems in the development of depression.