The new study published in the journal Psychopharmacology noted that research into the role of frustration and substance use disorders is sparse, but a number of studies suggest that persons with substance use disorders have lower frustration tolerance.

Studies have shown that sensitivity to frustration correlates with relapse among those with substance use disorders.

For the latest study, the researchers used a rat model to focus on frustration-related behaviour.

"An example of frustration behaviour is when someone can't get the channel on the TV to change or when an elevator takes too long to arrive. People will often respond to both situations by pressing the button repeatedly or holding the button longer with repeated attempts," said Thomas Green from The University of Texas Medical Branch at Galveston (UTMB).

"This typical human response to frustration is the same in rats. In our study, rats were trained to press a lever for delivery of either a sucrose pellet or an intravenous infusion of a synthetic opioid. If they didn't get what they expected, they would press the lever more frequently and for longer periods of time."

The study showed all rats would press a lever for intravenous infusions of fentanyl, a synthetic opioid, but about 10 per cent of rats would escalate their intake of fentanyl to about double that of the average rat, said Tileena Vasquez, a doctoral candidate at UTMB and the lead author of the paper.

"Even as the escalating rats take massive amounts of drug, their bar presses get longer (in some cases up to 10 minutes long), even though long bar presses do not increase the amount of drug delivered," Vasquez said.

The study has obvious implications for future studies of opioid use disorder and will help scientists understand how frustration, as well as craving, impulsivity and habit can lead to opioid escalation, said Green.