Stress can be detrimental to health and cognitive ability if the stressors are prolonged or severe. In many human studies on the effects of drugs, for instance, one factor that is often neglected is that the person taking the drugs is under stress. In addition, a recognized cause of relapse in addicts is being in stressful situations. Stress can be thought of as any threat, real or perceived, to well-being that drives an organism from homeostasis. We are interested in whether certain types of chronic developmental stress may result in long-term cognitive impairments.

In most situations the body’s response to stress is appropriate − an increased release of hormones from the hypothalamic-pituitary-adrenal axis that prepares the organism to respond to the threat and culminates with the release of cortisol in humans or corticosterone in rodents. Sympathetic activation also occurs with increases in epinephrine and norepinephrine from the adrenal glands. These hormones prepare the body for “fight or flight” responses so that essential organs have the necessary energy to protect themselves from danger to survive.

Eventually, when the stressor is removed, the body returns to a steady-state through negative feedback in which the released hormones act upon glucocorticoid and other receptors in the brain and pituitary to terminate further hormone release. However, if the stressor is prolonged, the hormones that were once important for survival become detrimental. The glucocorticoids (cortisol and corticosterone in particular) have neurotoxic effects in the brain when exposure to them is chronic.

We have recently taken a model of early stress used by other scientists and extended it to provide prolonged developmental stress. Rats show cognitive impairments as adults long after the stress is over. We are investigating whether this method might serve as a model of adult neuropsychiatric disorders related to mood and impaired cognitive function.