A behavioral timing intervention upregulates striatal serotonergic markers and reduces impulsive action in adult male mice.

Many studies support the hypothesis that time-based interventions reduce impulsive behavior in rodents. However, few studies have directly assessed 1) how such interventions affect impulsive action rather than impulsive choice, 2) if intervention effects differ by sex, and 3) how time-based interventions affect neurochemistry in regions mediating decision-making and reward. Thus, we assessed how a fixed-interval (FI) intervention initiated during late adolescence and extending into adulthood affected dopaminergic and serotonergic analytes in the frontal cortex and striatum and subsequent impulsive action in adult male and female mice. Beginning on postnatal day (PND) 45, mice were either trained on a progressive series of FI schedules (FI 20, 40, & 60 s) or remained in the home cage. Following the intervention, increases in striatal serotonergic analytes were found in FI-exposed males and females (n = 8/sex/group) with few changes found in the frontal cortex. Impulsive action was assessed in the remaining mice (n = 10/sex/group) using a fixed-ratio waiting-for-reward (FR-wait) task in which completion of an FR-25 component initiated a "free" pellet component in which pellets were delivered at increasing intervals according to a fixed delay increment that varied across sessions. Responses reset the additive delay and initiated a new FR-25 component. FI-exposed males, but not females, showed fewer delay resets and no-wait resets relative to control mice. Importantly, FI-exposure did not affect discrimination reversal performance in either sex. These data suggest that time-based interventions may reduce impulsive action in addition to impulsive choice perhaps with increased male sensitivity. Additionally, time-based interventions appear to operate through striatal serotonergic augmentation.