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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.

Air pollution (AP) is becoming recognized as a major threat to neurological health across the lifespan with increased risk of both neurodevelopmental and neurodegenerative disorders. AP is a complex mixture of gases and particulate matter, with adsorbed contaminants including metals and trace elements, which may differentially contribute to its neurodevelopmental impacts. Iron (Fe) is one of the most abundant metals found in AP, and Fe concentrations may drive some behavioral deficits observed in children. Furthermore, brains of neonate mice exposed to concentrated ambient ultrafine particulate matter (UFP) show significant brain accumulation of Fe and sulfur (S) supporting the hypothesis that AP exposure may lead to brain metal dyshomeostasis. The current study determined the extent to which behavioral effects of UFP, namely memory deficits and impulsive-like behavior, could be recapitulated with exposure to Fe aerosols with or without concomitant SO

Intermittent schedules of reinforcement define the conditions under which learned operant behavior is rewarded. Such schedules offer the opportunity to examine toxicant-induced changes in a variety of behavioral processes, including learning, attention and memory processes, sensory function, motor behavior and motivational states, thus providing critical information about risks arising from toxicant exposure and potential mechanisms of those effects. Such behavior is stable over extended periods of time, allowing for determination of time course of toxicant effects and reversibility. Importantly, schedule-controlled behavior generally shows considerable cross-species generality, facilitating the interpretation of toxicant-induced risks.

The glutamatergic (NMDA) and cholinergic neurotransmitter systems have been extensively implicated as neurochemical mediators of learning processes. These two systems may differentially affect learning; for example, although both the cholinergic antagonist scopolamine and the NMDA antagonist MK-801 reduced overall accuracy of rats in a 3-member repeated acquisition paradigm, the nature of the underlying error patterns produced by the two drugs differed significantly: rats administered scopolamine produced a pattern of skipping errors, while administration of MK-801 predominantly increased perseverative errors (Cohn et al., 1992). The present experiment extended that study to examine whether a more complex task, i.e. a 4-member repeated acquisition paradigm, would alter the nature of the error patterns resulting from administration of each drug, and whether NMDA itself would increase accuracy on the repeated acquisition paradigm. MK-801 (0.05-0.3mg/kg i.p.) significantly decreased overall accuracy in a dose-dependent manner, and the rats produced a pattern of errors similar, although not identical to, that noted in the 3-member paradigm, including perseverative errors early in the sequence, but additional skipping errors at later points in the sequence. MK-801 dramatically decreased correct initiation of a sequence following an error at any point in the sequence. NMDA (10.0-30.0mg/kg) itself did not facilitate sequence acquisition, i.e. it did not affect overall accuracy. However, it was the only drug to increase the frequency of correctly reinitiating a sequence following an incorrect first or an incorrect second sequence member. Like MK-801, scopolamine (0.5-3.0mg/kg i.p.) also produced a decline in overall accuracy which was again achieved primarily through increased skipping errors. Scopolamine did not, however, interfere with correctly reinitiating a sequence either after successful completion of a sequence, or after an error. These findings suggest that cholinergic and glutamatergic compounds exert their effects on learning through different behavioral mechanisms.