Aberrant glutamatergic systems underlying impulsive behaviors: Insights from clinical and preclinical research.

Impulsivity is a broad construct that often refers to one of several distinct behaviors and can be measured with self-report questionnaires and behavioral paradigms. Several psychiatric conditions are characterized by one or more forms of impulsive behavior, most notably the impulsive/hyperactive subtype of attention-deficit/hyperactivity disorder (ADHD), mood disorders, and substance use disorders. Monoaminergic neurotransmitters are known to mediate impulsive behaviors and are implicated in various psychiatric conditions. However, growing evidence suggests that glutamate, the major excitatory neurotransmitter of the mammalian brain, regulates important functions that become dysregulated in conditions like ADHD. The purpose of the current review is to discuss clinical and preclinical evidence linking glutamate to separate aspects of impulsivity, specifically motor impulsivity, impulsive choice, and affective impulsivity. Hyperactive glutamatergic activity in the corticostriatal and the cerebro-cerebellar pathways are major determinants of motor impulsivity. Conversely, hypoactive glutamatergic activity in frontal cortical areas and hippocampus and hyperactive glutamatergic activity in anterior cingulate cortex and nucleus accumbens mediate impulsive choice. Affective impulsivity is controlled by similar glutamatergic dysfunction observed for motor impulsivity, except a hyperactive limbic system is also involved. Loss of glutamate homeostasis in prefrontal and nucleus accumbens may contribute to motor impulsivity/affective impulsivity and impulsive choice, respectively. These results are important as they can lead to novel treatments for those with a condition characterized by increased impulsivity that are resistant to conventional treatments.

Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.

Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear. In this study, we used a food reward delay-discounting task (DDT) to identify low- and high-impulsive rats, in which low-impulsive rats exhibited preference for large delayed reward over small immediate rewards, while high-impulsive rats showed the opposite preference. We then examined D1, D2, and D3 receptor gene expression using RNAscope in situ hybridization assays. We found that high-impulsive male rats exhibited lower levels of D2 and D3, and particularly D3, receptor expression in the nucleus accumbens (NAc), with no significant changes in the insular, prelimbic, and infralimbic cortices. Based on these findings, we further explored the role of the D3 receptor in impulsive decision-making. Systemic administration of a selective D3 receptor agonist (FOB02-04) significantly reduced impulsive choices in high-impulsive rats but had no effects in low-impulsive rats. Conversely, a selective D3 receptor antagonist (VK4-116) produced increased both impulsive and omission choices in both groups of rats. These findings suggest that impulsive decision-making is associated with a reduction in D3 receptor expression in the NAc. Selective D3 receptor agonists, but not antagonists, may hold therapeutic potentials for mitigating impulsivity in high-impulsive subjects.

Behavioral and neuronal extracellular vesicle biomarkers associated with nicotine's enhancement of the reinforcing strength of cocaine in female and male monkeys.

While the majority of people with cocaine use disorders (CUD) also co-use tobacco/nicotine, most preclinical cocaine research does not include nicotine. The present study examined nicotine and cocaine co-use under several conditions of intravenous drug self-administration in monkeys, as well as potential peripheral biomarkers associated with co-use. In Experiment 1, male rhesus monkeys (N = 3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and with nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward/upward shift in the number of injections received. In Experiment 2, socially housed female and male cynomolgus monkeys (N = 14) self-administered cocaine under a concurrent drug-vs-food choice schedule of reinforcement. Adding nicotine to the cocaine solution shifted the cocaine dose-response curves to the left, with more robust shifts noted in the female animals. There was no evidence of social rank differences. To assess reinforcing strength, delays were added to the presentation of drug; the co-use of nicotine and cocaine required significantly longer delays to decrease drug choice, compared with cocaine alone. Blood samples obtained post-session were used to analyze concentrations of neuronally derived small extracellular vesicles (NDE); significant differences in NDE profile were observed for kappa-opioid receptors when nicotine and cocaine were co-used compared with each drug alone and controls. These results suggest that drug interactions involving the co-use of nicotine and cocaine are not simply changing potency, but rather resulting in changes in reinforcing strength that should be utilized to better understand the neuropharmacology of CUD and the evaluation of potential treatments.

Imagine before you leap: Episodic future thinking combined with transcranial direct current stimulation training for impulsive choice in repetitive negative thinking.

Background: Immediate reward preference in repetitive negative thinking (RNT) has a high clinical correlation with a variety of maladaptive behaviors, whereas episodic future thinking (EFT) may be conducive to dealing with non-adaptive thinking and decision-making. Objectives: This study aimed to evaluate the efficacy of EFT training combined with transcranial direct current stimulation (tDCS) stimulation over the ventromedial PFC (vmPFC) in inhibiting impulsive choice of RNT individuals. Method: Study 1 explored the effects of EFT on immediate reward preference of participants with high and low RNT (N = 48). Study 2 conducted a randomized controlled trial (RCT) to examine the treatment effect of the EFT-neural training on impulsive choice of high RNT individuals (N = 103). Results: In study 1, individuals with high RNT were more likely to choose smaller and sooner (SS) rewards, however, there were no significant differences between the high-RNT group and the low-RNT group under the positive EFT condition. In study 2, a significant decrease was shown in the proportion of choosing SS rewards under the 8-week EFT-neural training, and the effect was maintained at 1 month follow-up. Conclusion: RNT is a vulnerability factor for short-sighted behaviors, and EFT-neural training could be suitable for reducing RNT and improving immediate reward preference.

More widespread and rigid neuronal representation of reward expectation underlies impulsive choices.

Impulsive choices prioritize smaller, more immediate rewards over larger, delayed, or potentially uncertain rewards. Impulsive choices are a critical aspect of substance use disorders and maladaptive decision-making across the lifespan. Here, we sought to understand the neuronal underpinnings of expected reward and risk estimation on a trial-by-trial basis during impulsive choices. To do so, we acquired electrical recordings from the human brain while participants carried out a risky decision-making task designed to measure choice impulsivity. Behaviorally, we found a reward-accuracy tradeoff, whereby more impulsive choosers were more accurate at the task, opting for a more immediate reward while compromising overall task performance. We then examined how neuronal populations across frontal, temporal, and limbic brain regions parametrically encoded reinforcement learning model variables, namely reward and risk expectation and surprise, across trials. We found more widespread representations of reward value expectation and prediction error in more impulsive choosers, whereas less impulsive choosers preferentially represented risk expectation. A regional analysis of reward and risk encoding highlighted the anterior cingulate cortex for value expectation, the anterior insula for risk expectation and surprise, and distinct regional encoding between impulsivity groups. Beyond describing trial-by-trial population neuronal representations of reward and risk variables, these results suggest impaired inhibitory control and model-free learning underpinnings of impulsive choice. These findings shed light on neural processes underlying reinforced learning and decision-making in uncertain environments and how these processes may function in psychiatric disorders.

A systematic review and meta-analysis of test-retest reliability and stability of delay and probability discounting.

In this meta-analysis, we describe a benchmark value of delay and probability discounting reliability and stability that might be used to (a) evaluate the meaningfulness of clinically achieved changes in discounting and (b) support the role of discounting as a valid and enduring measure of intertemporal choice. We examined test-retest reliability, stability effect sizes (dz; Cohen, 1992), and relevant moderators across 30 publications comprising 39 independent samples and 262 measures of discounting, identified via a systematic review of PsychInfo, PubMed, and Google Scholar databases. We calculated omnibus effect-size estimates and evaluated the role of proposed moderators using a robust variance estimation meta-regression method. The meta-regression output reflected modest test-retest reliability, r = .670, p < .001, 95% CI [.618, .716]. Discounting was most reliable when measured in the context of temporal constraints, in adult respondents, when using money as a medium, and when reassessed within 1 month. Testing also suggested acceptable stability via nonsignificant and small changes in effect magnitude over time, dz = 0.048, p = .31, 95% CI [-0.051, 0.146]. Clinicians and researchers seeking to measure discounting can consider the contexts when reliability is maximized for specific cases.

Self-Control Training: A Scoping Review.

We conducted a scoping review of the behavior analytic self-control training (SCT) literature. To identify included articles, we searched key terms in six databases for articles published between 1988 and 2021. We included empirical articles that used a behavioral approach to self-control training with human participants for whom increasing self-control choice was a clinically significant goal and measured self-control and impulsive choice as dependent variables. Twenty-five experiments from 24 articles with a total of 79 participants were included in the review. This review aims to summarize the characteristics of SCT procedures and outcomes, provide recommendations for future research directions, and offer practical suggestions to clinicians incorporating SCT into practice. We examined similarities across studies regarding the independent variables manipulated in SCT, dependent variables measured, metrics of successful interventions, and assessment of generalization and maintenance of self-control choice. Twenty-one experiments arranged concurrent self-control- and impulsive-choice options with positive reinforcement, and four experiments arranged self-control training with negative-reinforcement contingencies. Variations of SCT included progressively increasing delays, intervening activities, signaled delays, antecedent rules, and commitment responses. Providing an intervening activity during the delay was largely successful at increasing self-control choice. Maintenance and generalization of increased self-control choice were assessed in two and three experiments, respectively. Future research should focus on improving the generality of SCT procedures in clinical settings by increasing terminal delays, fading out intervening activities, including probabilistic outcomes, and combining appetitive and aversive outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-023-00885-y.

Active and passive waiting in impulsive choice: Effects of fixed-interval and fixed-time delays.

Behavioral interventions to improve self-control, preference for a larger-later (LL) reward over a smaller-sooner (SS) reward, involve experience with delayed rewards. Whether they involve timing processes remains controversial. In rats, there have been inconsistent results on whether timing processes may be involved in intervention-induced improvements in self-control. Interventions that improved self-control with corresponding timing improvements used fixed-interval (FI) delays, whereas interventions that failed to find corresponding timing improvements used fixed-time (FT) delays. The FI schedule includes a response contingency (active waiting), whereas the FT schedule delivers reward automatically (passive waiting). The present study compared the effects of FI and FT schedules in interventions and impulsive choice tasks to evaluate effects on self-control and timing behavior. The impulsive choice task evaluated preference for an SS option (one pellet after 10-, 15-, 20-, 25-, and 30-s delays) versus an LL option (two pellets after a 30-s delay). The intervention task included forced-choice SS (one pellet after 10 s) and LL (two pellets after 30 s) sessions under FI or FT schedules. FI schedules produced greater sensitivity to SS delay in the impulsive choice task. Both FI and FT interventions increased LL choices. Following choice testing, temporal bisection and peak interval tasks revealed better timing precision for rats with an FI delay experience. Overall, the FI choice contingency was associated with improved temporal attention and timing precision.

Laboratory method to induce state boredom increases impulsive choice in people who use cocaine and controls.

Background: Impulsive choice is associated with both cocaine use and relapse. Little is known about the influence of transient states on impulsive choice in people who use cocaine (PWUC).Objective: This study investigated the direct effects of induced boredom on impulsive choice (i.e., temporal discounting) in PWUC relative to well-matched community controls.Methods: Forty-one PWUC (≥1× cocaine use in past 3 months; 7 females) and 38 demographically matched controls (5 females) underwent two experimental conditions in counterbalanced order. Temporal discounting was assessed immediately after a standardized boredom induction task (peg-turning) and a self-selected video watched for the same duration (non-boredom). Subjective mood state and perceived task characteristics were assessed at baseline, during experimental manipulations, and after the choice task.Results: PWUC and controls were well matched on sex, age, and socioeconomic status. Groups were also similar in reported use of drugs other than cocaine, except for recent cigarette and alcohol use (PWUC > controls). As expected, peg-turning increased boredom in the sample overall, with higher boredom reported during peg-turning than the video (p < .001, η2p = .20). Participants overall exhibited greater impulsive choice after boredom than non-boredom (p = .028, η2p = .07), with no preferential effects in PWUC (p > .05, BF01 = 2.9).Conclusion: Experimentally induced boredom increased state impulsivity irrespective of cocaine use status - in PWUC and carefully matched controls - suggesting a broad link between boredom and impulsive choice. This is the first study to show that transient boredom directly increases impulsive choice. Data support a viable laboratory method to further parse the effects of boredom on impulsive choice.

Motor impulsivity but not risk-related impulsive choice is associated to drug intake and drug-primed relapse.

Introduction: Motor impulsivity and risk-related impulsive choice have been proposed as vulnerability factors for drug abuse, due to their high prevalence in drug abusers. However, how these two facets of impulsivity are associated to drug abuse remains unclear. Here, we investigated the predictive value of both motor impulsivity and risk-related impulsive choice on characteristics of drug abuse including initiation and maintenance of drug use, motivation for the drug, extinction of drug-seeking behavior following drug discontinuation and, finally, propensity to relapse. Methods: We used the Roman High- (RHA) and Low- Avoidance (RLA) rat lines, which display innate phenotypical differences in motor impulsivity, risk-related impulsive choice, and propensity to self-administer drugs. Individual levels of motor impulsivity and risk-related impulsive choice were measured using the rat Gambling task. Then, rats were allowed to self-administer cocaine (0.3 mg/kg/infusion; 14 days) to evaluate acquisition and maintenance of cocaine self-administration, after which motivation for cocaine was assessed using a progressive ratio schedule of reinforcement. Subsequently, rats were tested for their resistance to extinction, followed by cue-induced and drug-primed reinstatement sessions to evaluate relapse. Finally, we evaluated the effect of the dopamine stabilizer aripiprazole on reinstatement of drug-seeking behaviors. Results: We found that motor impulsivity and risk-related impulsive choice were positively correlated at baseline. Furthermore, innate high levels of motor impulsivity were associated with higher drug use and increased vulnerability to cocaine-primed reinstatement of drug-seeking. However, no relationships were observed between motor impulsivity and the motivation for the drug, extinction or cue-induced reinstatement of drug-seeking. High levels of risk-related impulsive choice were not associated to any aspects of drug abuse measured in our study. Additionally, aripiprazole similarly blocked cocaine-primed reinstatement of drug-seeking in both high- and low-impulsive animals, suggesting that aripiprazole acts as a D2/3R antagonist to prevent relapse independently of the levels of impulsivity and propensity to self-administer drugs. Discussion: Altogether, our study highlights motor impulsivity as an important predictive factor for drug abuse and drug-primed relapse. On the other hand, the involvement of risk-related impulsive choice as a risk factor for drug abuse appears to be limited.

Mechanisms of impulsive choice: Experiments to explore and models to map the empirical terrain.

Impulsive choice is preference for a smaller-sooner (SS) outcome over a larger-later (LL) outcome when LL choices result in greater reinforcement maximization. Delay discounting is a model of impulsive choice that describes the decaying value of a reinforcer over time, with impulsive choice evident when the empirical choice-delay function is steep. Steep discounting is correlated with multiple diseases and disorders. Thus, understanding the processes underlying impulsive choice is a popular topic for investigation. Experimental research has explored the conditions that moderate impulsive choice, and quantitative models of impulsive choice have been developed that elegantly represent the underlying processes. This review spotlights experimental research in impulsive choice covering human and nonhuman animals across the domains of learning, motivation, and cognition. Contemporary models of delay discounting designed to explain the underlying mechanisms of impulsive choice are discussed. These models focus on potential candidate mechanisms, which include perception, delay and/or reinforcer sensitivity, reinforcement maximization, motivation, and cognitive systems. Although the models collectively explain multiple mechanistic phenomena, there are several cognitive processes, such as attention and working memory, that are overlooked. Future research and model development should focus on bridging the gap between quantitative models and empirical phenomena.

Effects of the estrous cycle on impulsive choice and interval timing in female rats.

Research in humans and animals shows differences in impulsive choice, which is a failure to wait for larger, delayed rewards, when comparing males and females. It is possible that fluctuations in sex hormones (estradiol and progesterone) across the reproductive cycle contribute to sex differences in impulsive choice. The current study delivered an impulsive choice task with peak interval trials to female rats while estrous cycles, the rodent reproductive cycle, were tracked over the course of the task. Female rats were more sensitive to changes in delay in the proestrus phase of the estrous cycle and made more larger-later choices when in estrus, particularly when the delay to the smaller reward was short. Estradiol increases dramatically during proestrus while progesterone peaks during estrus, suggesting that estradiol and progesterone may affect impulsive choice through mechanisms such as delay discounting, delay aversion, and/or timing processes. Analyses of timing of the choice task delays showed inconsistent effects of the estrous cycle across delays, suggesting that reward-timing interactions may have complicated how hormone fluctuations affected interval timing. Further research is needed to determine the mechanism underlying increased larger-later choices during the estrus phase, increased delay sensitivity during the proestrus phase, and variability in interval timing across delays and estrous cycle stages.

Concurrent measures of impulsive action and choice are partially related and differentially modulated by dopamine D1- and D2-like receptors in a rat model of impulsivity.

Impulsivity is a multidimensional construct, but the relationships between its constructs and their respective underlying dopaminergic underpinnings in the general population remain unclear. A cohort of Roman high- (RHA) and low- (RLA) avoidance rats were tested for impulsive action and risky decision-making in the rat gambling task, and then for delay discounting in the delay-discounting task to concurrently measure the relationships among the three constructs of impulsivity using a within-subject design. Then, we evaluated the effects of dopaminergic drugs on the three constructs of impulsivity, considering innate differences in impulsive behaviors at baseline. Risky decision-making and delay-discounting were positively correlated, indicating that both constructs of impulsive choice are related. Impulsive action positively correlated with risky decision-making but not with delay discounting, suggesting partial overlap between impulsive action and impulsive choice. RHAs showed a more impulsive phenotype in the three constructs of impulsivity compared to RLAs, demonstrating the comorbid nature of impulsivity in a population of rats. Amphetamine increased impulsive action and had no effect on risky decision-making regardless of baseline levels of impulsivity, but it decreased delay discounting only in high impulsive RHAs. In contrast, while D1R and D3R agonism as well as D2/3R partial agonism decreased impulsive action regardless of baseline levels of impulsivity, D2/3R agonism decreased impulsive action exclusively in high impulsive RHAs. Irrespective of baseline levels of impulsivity, risky decision-making was increased by D1R and D2/3R agonism but not by D3R agonism or D2/3R partial agonism. Finally, while D1R and D3R agonism, D2/3R partial agonism and D2R blockade increased delay discounting irrespective of baseline levels of impulsivity, D2/3R agonism decreased it in low impulsive RLAs only. These findings indicate that the acute effects of dopamine drugs were partially overlapping across dimensions of impulsivity, and that only D2/3R agonism showed baseline-dependent effects on impulsive action and impulsive choice.

A Proof-of-Concept Ecological Momentary Assessment Study of Day-Level Dynamics in Value-Based Decision-Making in Opioid Addiction.

Background: Drug addiction is thought to be characterized by risky and impulsive behavior despite harmful consequences. Whether these aspects of value-based decision-making in people with addiction are stable and trait-like, and the degree to which they vary within-person and are sensitive to changes in psychological state, remains unknown. In this pilot study, we examined the feasibility of distinguishing these state- vs. trait-like components by probing day-level dynamics of risk and time preferences in patients with opioid use disorder (OUD) as they engaged with their natural environment. Methods: Twenty-three individuals with OUD receiving outpatient treatment (40% female; M = 45.67 [SD = 13.16] years of age) and twenty-one matched healthy community controls (47% female; M = 49.67 [SD = 14.38] years of age) participated in a 28-day smartphone-based ecological momentary assessment study (1085 person days; M = 24.66, SD = 5.84). Random prompts administered daily assessed subjects' psychological state (e.g., mood) and economic preferences for real delayed and risky monetary rewards. Results: Subjects demonstrated dynamic decision-making preferences, with 40-53% of the variation in known risk and ambiguity tolerance, and 67% in discounting, attributable to between-person vs. within-person (day-to-day) differences. We found that changes in psychological state were related to changes in risk preferences, with patients preferring riskier offers on days they reported being in a better mood but no differences between groups in aggregate level behavior. By contrast, temporal discounting was increased overall in patients compared to controls and was unrelated to global mood. The study was well-tolerated, but compliance rates were moderate and lower in patients. Conclusion: Our data support the idea that decision-making preferences in drug addiction exhibit substantial within-person variability and that this variability can be well-captured using remote data collection methods. Preliminary findings suggested that aspects of decision-making related to consideration of risk may be more sensitive to within-person change in global psychological state while those related to consideration of delay to reward, despite also being somewhat variable, stably differ from healthy levels. Identifying the cognitive factors that contribute to opioid use risk in a "real-world" setting may be important for identifying unique, time-sensitive targets for intervention.

A method for studying reinforcement factors controlling impulsive choice for use in behavioral neuroscience.

Although procedures originating within the experimental analysis of behavior commonly are used in behavioral neuroscience to produce behavioral endpoints, they are used less often to analyze the behavioral processes involved, particularly at the level of individual organisms (see Soto, 2020). Concurrent-chains procedures have been used extensively to study choice and to quantify relations between various dimensions of reinforcement and preference. Unfortunately, parametric analysis of those relations using traditional steady-state, single-subject experimental designs can be time-consuming, often rendering these procedures impractical for use in behavioral neuroscience. The purpose of this paper is to describe how concurrent-chains procedures can be adapted to allow for parametric examination of effects of the reinforcement dimensions involved in impulsive choice (magnitude and delay) within experimental sessions in rats. Data are presented indicating that this procedure can produce relatively consistent within-session estimates of sensitivity to reinforcement in individual subjects, and that these estimates can be modified by neurobiological manipulation (drug administration). These data suggest that this type of procedure offers a promising approach to the study of neurobiological mechanisms of complex behavior in individual organisms, which could facilitate a more fruitful relationship between behavior analysis and behavioral neuroscience.

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives.

Fluctuating ovarian hormones have been shown to affect decision-making processes in women. While emerging evidence suggests effects of endogenous ovarian hormones such as estradiol and progesterone on value-based decision-making in women, the impact of exogenous synthetic hormones, as in most oral contraceptives, is not clear. In a between-subjects design, we assessed measures of value-based decision-making in three groups of women aged 18 to 29 years, during (1) active oral contraceptive intake (N = 22), (2) the early follicular phase of the natural menstrual cycle (N = 20), and (3) the periovulatory phase of the natural menstrual cycle (N = 20). Estradiol, progesterone, testosterone, and sex-hormone binding globulin levels were assessed in all groups via blood samples. We used a test battery which measured different facets of value-based decision-making: delay discounting, risk-aversion, risk-seeking, and loss aversion. While hormonal levels did show the expected patterns for the three groups, there were no differences in value-based decision-making parameters. Consequently, Bayes factors showed conclusive evidence in support of the null hypothesis. We conclude that women on oral contraceptives show no differences in value-based decision-making compared to the early follicular and periovulatory natural menstrual cycle phases.

Reducing impulsive choice: VIII. Effects of delay-exposure training in female rats.

Impulsive choice may play an important role in serious health-related decisions, like addiction tendencies. Thus, there is merit in exploring interventions that reduce impulsive choice. Delay-exposure training involves extended experience with delayed reinforcement. Following training, delay-exposed rats make fewer impulsive choices than control rats. The reducing effects of delay exposure training on impulsive choice have been replicated in male rats seven times. For the first time, this study evaluated the effects of delay exposure training in female rats. Thirty-six rats were randomly assigned to either delay-exposure or immediacy-exposure training. Then, rats underwent two impulsive choice assessments in which they chose between one immediate pellet or three delayed pellets. In the first assessment, delays increased within-sessions, across trial blocks from 0, 8, 16, to 32 s. In the second assessment, delays to the larger reward increased between-sessions, from 8, 16, 32, to 4 s. Unlike findings with male rats, delay-exposure training produced a reduction in impulsive choice only in the initial five sessions in female rats. Possible reasons for the lack of lasting effect in female rats are discussed and future research directions are identified.

GABAB receptors in prelimbic cortex and basolateral amygdala differentially influence intertemporal decision making and decline with age.

The ability to decide adaptively between immediate vs. delayed gratification (intertemporal choice) is critical for well-being and is associated with a range of factors that influence quality of life. In contrast to young adults, many older adults show enhanced preference for delayed gratification; however, the neural mechanisms underlying this age difference in intertemporal choice are largely un-studied. Changes in signaling through GABAB receptors (GABABRs) mediate several age-associated differences in cognitive processes linked to intertemporal choice. The current study used a rat model to determine how GABABRs in two brain regions known to regulate intertemporal choice (prelimbic cortex; PrL and basolateral amygdala; BLA) contribute to age differences in this form of decision making in male rats. As in humans, aged rats showed enhanced preference for large, delayed over small, immediate rewards during performance in an intertemporal choice task in operant test chambers. Activation of PrL GABABRs via microinfusion of the agonist baclofen increased choice of large, delayed rewards in young adult rats but did not influence choice in aged rats. Conversely, infusion of baclofen into the BLA strongly reduced choice of large, delayed rewards in both young adult and aged rats. Aged rats further showed a significant reduction in expression of GABABR1 subunit isoforms in the prefrontal cortex, a discovery that is consonant with the null effect of intra-PrL baclofen on intertemporal choice in aged rats. In contrast, expression of GABABR subunits was generally conserved with age in the BLA. Jointly, these findings elucidate a role for GABABRs in intertemporal choice and identify fundamental features of brain maturation and aging that mediate an improved ability to delay gratification.

Generalizability of time-based interventions: Effects of choice procedure and smaller-sooner delay.

Interventions exposing rats to delayed-reward contingencies attenuate suboptimal impulsive choices, a preference for a smaller-sooner (SS) over a larger-later (LL) reward. Interventions may potentially improve delay-tolerance, timing of delays, and/or discrimination of reward magnitudes. Generalization from the intervention to impulsive choice under different procedures can provide insights into the processes that underlie the intervention effects. Experiment 1 tested intervention effects on systematic-delay (SYS) and adjusting-delay (ADJ) procedures, predicting that intervention effects would be more effective on the SYS procedure with predictable delays. The ADJ procedure did not benefit significantly from intervention, but the SYS procedure, unexpectedly, showed greater impulsive choices following intervention. Experiment 2 tested whether short (5 s) SS intervention delays may have promoted greater impulsivity in the SYS impulsive choice procedure in Experiment 1. Short SS delays in choice and intervention procedures increased impulsive choices in comparison to longer (10 s) delays. Incongruent SS delays in the intervention/choice procedures resulted in negative intervention effects. The results suggest that short SS delays are detrimental to self-control and that specific temporal information generalizes from the intervention to the SYS choice task, but not the ADJ choice task.

Effects of immediate-reinforcement training on delay discounting behavior in rats.

Chronic exposure to delayed reinforcement has been shown to increase choice for larger, later reinforcement in a subsequent delay discounting task. In the three experiments presented in this paper, the opposite was tested: effects of chronic exposure to immediate reinforcement on choice in a subsequent delay discounting task. In Experiment 1, larger, later reinforcement choice was significantly reduced as a result of exposure to immediate reinforcement, compared to a maturation/handle control group, in experienced, male Lewis rats. In Experiment 2, with naive male and female Wistar rats, and Experiment 3, with naïve male Long Evans rats, the impact of exposure to immediate reinforcement was less robust, but directionally consistent with results from Experiment 1. These results align with some previous work reporting that exposure to immediate reinforcement may decrease choice for larger, later reinforcement in a delay discounting task, and/or blunt maturational increases in choice for larger, later reinforcement. These findings have implications for future research investigating experience-based interventions to manipulate delay discounting behavior. They also have clinical implications for understanding and treating disorders involving maladaptive choice.