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Researchers have found that long-term (chronic) treatment with opioids, such as morphine, prior to trauma may increase post-traumatic stress disorder (PTSD) risk.
The findings, published in the journal Neuropsychopharmacology, which link chronic opioid treatment before a traumatic event with responses to subsequent stressful events, may suggest a possible mechanism underlying the frequent co-occurrence of post-traumatic stress disorder (PTSD) and opioid dependence.
"Our data are the first to show a possible effect of opioids on future fear learning, which may suggest that a person with a history of opioid use may become more susceptible to the negative effects of stress," said study researcher Michael Fanselow from University of California in the US.
"Also, this ability of opioids to increase PTSD-like symptoms far outlasted the direct effects of the drug or withdrawal from the drug, suggesting that the effect may continue even after opioid treatment has stopped," Fanselow added.
Previous research has shown that PTSD increases the risk of opioid dependence, but whether opioid dependence may also increase PTSD risk remained unclear.
Using an established model of fear learning in mice, researchers assessed the potential impact of chronic opioid treatment on subsequent development of PTSD-like behaviours.
They found that mice that had been treated with opioids and later experienced stress showed more pronounced post-stress reactions.
At the beginning of the study, mice were treated with morphine or saline for eight days, followed by a week of drug cessation.
Both groups of mice - morphine-treated mice and saline-treated controls (22 and 24 mice, respectively) - were then subdivided into trauma and non-trauma groups.
They were transferred to a chamber where animals in the trauma group received a series of mild foot shocks. A day later, both groups of animals were returned to the chamber to assess their memory of the traumatic event.
"We have called this the trauma because the acute stressor, the foot shocks, is able to produce lasting fear and anxiety-like behaviours, such as freezing," Fanselow said.
On the subsequent day, mice from both the trauma and non-trauma groups were transferred to a new environment and exposed to a mild stressor (a milder foot shock), before being returned to that environment for eight minutes on the fourth day of the experiment.
The authors found no behavioural differences between morphine-treated and control mice following the initial trauma.
However, morphine-treated mice showed more pronounced freezing when returned to the second environment after having been exposed to the mild stressor.
The findings suggest that chronic exposure to opioids before - but not after - a traumatic event occurs, impacts fear learning during subsequent stressful events.