Females in the forefront: time-based intervention effects on impulsive choice and interval timing in female rats.

Impulsive choice has been implicated in substance abuse, gambling, obesity, and other maladaptive behaviors. Deficits in interval timing may increase impulsive choices, and therefore, could serve as an avenue through which suboptimal impulsive choices can be moderated. Temporal interventions have successfully attenuated impulsive choices in male rats, but the efficacy of a temporal intervention has yet to be assessed in female rats. As such, this experiment examined timing and choice behavior in female rats, and evaluated the ability of a temporal intervention to mitigate impulsive choice behavior. The temporal intervention administered in this study was successful in reducing impulsive choices compared to a control group. Results of a temporal bisection task indicated that the temporal intervention increased long responses at the shorter durations. Further, results from the peak trials within the choice task combined with the progressive interval task suggest that the intervention increased sensitivity to delay and enhanced timing confidence. Overall, these results indicate that a temporal intervention can be a successful avenue for reducing impulsive choice behavior in female rats, and could contribute to the development of behavioral interventions to prevent impulsive choice and maladaptive behaviors that can be applied to both sexes.

Durability and generalizability of time-based intervention effects on impulsive choice in rats.

Impulsive choice involves choosing a smaller-sooner (SS) reward over a larger-later (LL) reward. Due to the importance of timing processes in impulsive choice, time-based interventions have been developed to decrease impulsive choice. The present set of experiments assessed the durability and generalizability of time-based interventions. Experiment 1 assessed fixed interval (FI) or variable interval (VI) intervention efficacy over 9 months. The FI intervention decreased impulsive choice, and this effect persisted over time, but the VI intervention effects were only apparent when tested immediately after the intervention. Experiment 2 examined the generalizability of the FI and VI interventions on choice tasks manipulating the SS delay, LL delay, or LL magnitude. The FI intervention decreased sensitivity to delay, promoting LL choices in both delay tasks, but the VI intervention only altered choices when manipulating the SS delay. Experiment 3 further examined the FI intervention effects on tasks that manipulated the LL delay or magnitude immediately following the intervention. The intervention decreased sensitivity to both delay and magnitude. The experiments indicate that the FI intervention is effective at decreasing impulsive choice behavior for an extended period across changing delays and magnitudes, suggesting a relatively broad effect on choice behavior.

Nucleus accumbens core lesions induce sub-optimal choice and reduce sensitivity to magnitude and delay in impulsive choice tasks.

The nucleus accumbens core (NAc) has long been recognized as an important contributor to the computation of reward value that is critical for impulsive choice behavior. Impulsive choice refers to choosing a smaller-sooner (SS) over a larger-later (LL) reward when the LL is more optimal in terms of the rate of reward delivery. Two experiments examined the role of the NAc in impulsive choice and its component processes of delay and magnitude processing. Experiment 1 delivered an impulsive choice task with manipulations of LL reward magnitude, followed by a reward magnitude discrimination task. Experiment 2 tested impulsive choice under manipulations of LL delay, followed by temporal bisection and progressive interval tasks. NAc lesions, in comparison to sham control lesions, produced suboptimal preferences that resulted in lower reward earning rates, and led to reduced sensitivity to magnitude and delay within the impulsive choice task. The secondary tasks revealed intact reward magnitude and delay discrimination abilities, but the lesion rats persisted in responding more as the progressive interval increased during the session. The results suggest that the NAc is most critical for demonstrating good sensitivity to magnitude and delay, and adjusting behavior accordingly. Ultimately, the NAc lesions induced suboptimal choice behavior rather than simply promoting impulsive choice, suggesting that an intact NAc is necessary for optimal decision making.

The medial frontal cortex contributes to but does not organize rat exploratory behavior.

Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning.

Cholinergic deafferentation of the hippocampus causes non-temporally graded retrograde amnesia in an odor discrimination task.

Dementia of the Alzheimer's type (DAT) is a neurodegenerative disorder marked by loss of hippocampal cholinergic tone and significant memory impairments, specifically for memories acquired prior to disease onset. The nature of this relationship, however, remains debated. The current study used the string pulling task to evaluate the temporal effects of odor discrimination learning in animals with selective cholinergic lesions to determine the role of the septohippocampal cholinergic system in mnemonic function. Rats with 192-IgG-Saporin lesions to the medial septum had a higher number of correct responses in the reversal training when compared to sham rats, suggesting an inability to retrieve the previously learned discrimination; however, no temporal gradient was observed. Furthermore, there were no group differences when learning a novel odor discrimination, demonstrating the ability for all rats to form new memories. These results establish a role for the cholinergic medial septum projections in long-term memory retrieval. The current study provides a behavioral assessment technique to investigate factors that influence mnemonic deficits associated with rodent models of DAT.

I can't wait: Methods for measuring and moderating individual differences in impulsive choice.

Impulsive choice behavior occurs when individuals make choices without regard for future consequences. This behavior is often maladaptive and is a common symptom in many disorders, including drug abuse, compulsive gambling, and obesity. Several proposed mechanisms may influence impulsive choice behavior. These mechanisms provide a variety of pathways that may provide the basis for individual differences that are often evident when measuring choice behavior. This review provides an overview of these different pathways to impulsive choice, and the behavioral intervention strategies being developed to moderate impulsive choice. Because of the compelling link between impulsive choice behavior and the near-epidemic pervasiveness of obesity in the United States, we focus on the relationship between impulsive choice behavior and obesity as a test case for application of the multiple pathways approach. Choosing immediate gratification over healthier long term food choices is a contributing factor to the obesity crisis. Behavioral interventions can lead to more self controlled choices in a rat pre-clinical model, suggesting a possible gateway for translation to human populations. Designing and implementing effective impulsive choice interventions is crucial to improving the overall health and well-being of impulsive individuals.

Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function.

Degeneration of the septohippocampal system is associated with the progression of Dementia of the Alzheimer's type (DAT). Impairments in mnemonic function and spatial orientation become more severe as DAT progresses. Although evidence supports a role for cholinergic function in these impairments, relatively few studies have examined the contribution of the septohippocampal GABAergic component to mnemonic function or spatial orientation. The current study uses the rat food-hoarding paradigm and water maze tasks to characterize the mnemonic and spatial impairments associated with infusing GAT1-Saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). Although infusion of GAT1-Saporin significantly reduced parvalbumin-positive cells in the MS/VDB, no reductions in markers of cholinergic function were observed in the hippocampus. In general, performance was spared during spatial tasks that provided access to environmental cues. In contrast, GAT1-Saporin rats did not accurately carry the food pellet to the refuge during the dark probe. These observations are consistent with infusion of GAT1-Saporin into the MS/VDB resulting in spared mnemonic function and use of environmental cues; however, self-movement cue processing was compromised. This interpretation is consistent with a growing literature demonstrating a role for the septohippocampal system in self-movement cue processing.