Stress leads to drugs, leads to more stress and more drugs - part of a vicious cycle

Sep 1 2005

According to a new Australian study, opiate drugs such as morphine have been found to leave animals more vulnerable to stress, and this could mean stress and opiates are caught in a vicious cycle.

The study found that though stress triggered drug use, the drug left the animals more vulnerable to stress.

The study, by a team at the University of New South Wales, goes some way to explain why people who use opiates such as heroin have very high rates of anxiety problems, including post-traumatic stress disorder, even after they stop using, and that very fragile emotional state makes them more likely to start using again.

An understanding of how opiate users respond to and cope with stress could lead to better treatment and help prevent relapses.

Co-author Gavan McNally, PhD, says that heroin is the most commonly used illicit opiate, followed perhaps by morphine, while in medical settings, pethidine, fentanyl, morphine and codeine are typically used.

In their study McNally and his colleagues conducted four experiments with rats, injecting them with either morphine or saline solution every day for 10 days.

Then, either one or seven days after the final injection, they gently restrained each rat for 30 minutes as a form of stress.

The team then measured the rats' biological responses to the restraint stress. They also studied behaviors that reflect anxiety, checking the rats' levels of social interaction and general activity. The researchers tested anxiety responses for three different dose levels and different durations of exposure (0, 1, 5 or 10 days).

It was found that in the absence of stress, the opiate-treated rats were exactly the same as the control rats, and only when the animals were exposed to a stressor were there marked differences in nervous-system and behavioral responses.

The exposure to morphine left those rats significantly more anxious in response to stress. This effect was sensitive to both dose and duration: The longer the duration or the higher the dose of morphine, the greater the difference in anxiety between morphine and saline-treated rats.

According to the authors, this is the first important evidence that opiate use increases subsequent vulnerability to stress, which makes it a tough nut to crack given that stress leads to drug use.

The results also show for the first time that the vulnerability could last at least a week, evidence that the altered response was independent of any recent effect of the opiate or of opiate withdrawal.

Brief exposure to opiates, of five or fewer days, it seems was not enough to change vulnerability to stress, McNally says it appears the development of opiate dependence is the critical variable, and there are marked individual differences in humans in the development of dependence. He says a few days of codeine to relieve post-operative pain are unlikely to lead to the development of dependence.

McNally says rodent nervous systems are similar to humans which allows neuroscientists to study the behavioral and brain mechanisms for drug addiction.

The authors speculate that opiates may, by altering the expression of specific anxiety-related genes, prime the nervous system in a lasting way to be more vulnerable to stress, and notes the paradox that drugs used to escape from stress instead may heighten its impact.

The study appears in the current issue of the journal Behavioral Neuroscience, which is published by the American Psychological Association (APA).