A new study has found that opiate drugs such as morphine leave animals more vulnerable to stress. This means that stress and opiates are in a vicious cycle: Not only does stress trigger drug use, but in return the drug leaves animals more vulnerable to stress.
The study, conducted at the University of New South Wales, helps 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. That emotional fragility can also make them more likely to start using again.
The study appears in the current issue of the journal Behavioral Neuroscience, which is published by the American Psychological Association (APA). Understanding how opiate users respond to and cope with stress may lead to better treatment and help prevent relapses. Co-author Gavan McNally, PhD, notes that heroin is the most commonly used illicit opiate, followed perhaps by morphine. In medical settings, pethidine, fentanyl, morphine and codeine are typically used.
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).
In the absence of stress, the opiate-treated rats were exactly the same as the control rats. Only when the animals were exposed to a stressor were there marked differences in nervous-system and behavioral responses. For example, in terms of anxiety, the impact of stress was twice as great for the morphine-treated rats as for the saline-treated rats. Whereas stress reduced social interaction by about 31 percent in the saline-treated animals, it reduced social interaction by 68 percent in the morphine-treated animals.
Thus, 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.
The authors say this is the first important evidence that opiate use increases subsequent vulnerability to stress - a tough knot to untie given that stress leads to drug use. The results also were first to show 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.