Individual Differences in Frustrative Nonreward Behavior for Sucrose in Rats Predict Motivation for Fentanyl Under Progressive Ratio.

Frustrative nonreward is a construct in the Negative Valence Systems domain of the Research Domain Criteria (RDoC) from the US National Institute of Mental Health. An organism's response to frustrating situations (e.g. inability to obtain an expected reward) has broad implications for a variety of neuropsychiatric conditions, including substance use disorders. The current project developed a first of its kind rat operant behavioral model of frustrative nonreward based loosely on the human Point Subtraction Aggression Paradigm. The current study shows that individual differences in frustrative nonreward for sucrose pellets are consistent across sessions at baseline and that the task is sensitive to reward size in male rats. More importantly, high frustrative nonreward behavior for sucrose predicts early "breaking" for intravenous fentanyl self-administration under a progressive ratio schedule. These results solidify frustration/frustrative nonreward as an important factor for substance use disorders in addition to craving, impulsivity, and habit.Significance StatementThere are a few human studies that suggest that frustration behavior is a risk factor for substance use disorders. The present study focuses on rats' behavior during frustrative nonreward tasks in substance abuse-related operant procedures. These procedures utilized bar press durations which have been shown to be a measure of frustration-like behavior. Accordingly, the study found that individual differences in frustration-like behavior can be used predict drug seeking and taking. Thus, the results of this study support frustration as a 4th major facet of substance abuse-related behavior, adding to craving, impulsivity, and habit.