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

Frustrative nonreward (FN) is a construct in the Negative Valence Systems domain of the Research Domain Criteria (RDoC) from the 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 FN based loosely on the human Point Subtraction Aggression Paradigm (PSAP). The current study shows that individual differences in FN for sucrose pellets are consistent across sessions at baseline and that the task is sensitive to reward size in male rats. More importantly, high FN behavior for sucrose predicts early “breaking” for intravenous fentanyl self-administration under a progressive ratio (PR) schedule. These results solidify frustration/ FN as an important factor for substance use disorders in addition to craving, impulsivity, and habit.