Delay Discounting Task Research Articles

Neural Correlates of Delay Discounting in the Light of Brain Imaging and Non-Invasive Brain Stimulation: What We Know and What Is Missed.

In decision making, the subjective value of a reward declines with the delay to its receipt, describing a hyperbolic function. Although this phenomenon, referred to as delay discounting (DD), has been extensively characterized and reported in many animal species, still, little is known about the neuronal processes that support it. Here, after drawing a comprehensive portrait, we consider the latest neuroimaging and lesion studies, the outcomes of which often appear contradictory among comparable experimental settings. In the second part of the manuscript, we focus on a more recent and effective route of investigation: non-invasive brain stimulation (NIBS). We provide a comprehensive review of the available studies that applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to affect subjects' performance in DD tasks. The aim of our survey is not only to highlight the superiority of NIBS in investigating DD, but also to suggest targets for future experimental studies, since the regions considered in these studies represent only a fraction of the possible ones. In particular, we argue that, based on the available neurophysiological evidence from lesion and brain imaging studies, a very promising and underrepresented region for future neuromodulation studies investigating DD is the orbitofrontal cortex.

Optogenetic disruption of the prelimbic cortex alters long-term decision strategy but not valuation on a spatial delay discounting task

Rats demonstrate a preference for smaller, immediate rewards over larger, delayed ones, a phenomenon known as delay-discounting (DD). Behavior arises from the interaction of multiple decision-making systems, and the medial prefrontal cortex (mPFC) has been identified as a central component in the mediation between these decision systems. To investigate the role of the prelimbic (PL) subregion of mPFC on decision strategy interaction, we compared two cohorts of rats (ChR2-opsin-expressing ‘Active’ and opsin-absent ‘Control’) on a spatial delay-discounting task while delivering in-vivo light stimulation into PL at the choice point of select trials. By analyzing the overall delay-adjustment along with deliberative and procedural behavioral strategy markers, our study revealed differences in the decision strategies used between the active and control animals despite both groups showing similar valuations. Control animals developed the expected shift from deliberative to procedural decision strategy on this task (indicated by reaching delay-stability, particularly during late-session laps); however, active-virus animals repeatedly over-adjusted around their preferred delay throughout the entire session, suggesting a significant deficit in procedural decision-making on this task. Active animals showed a significant decrease in proportion of vicarious trial and error events (VTE, a behavior correlated with deliberative processes) on delay adjustment laps relative to control animals. This points to a more nuanced role for VTE, not just in executing deliberation, but in shifting from deliberative to procedural processes. This opto-induced change in VTE was especially pronounced for late-session adjustment laps. We found no other session-by-session or lap-by-lap effects, leaving a particular role for PL in the long-term development of procedural strategies on this task.

Rate-dependent effects of narrative interventions in a longitudinal study of individuals who use alcohol.

Delay discounting (DD), the decrease in reward valuation as a function of delay to receipt, is a key process undergirding alcohol use. Narrative interventions, including episodic future thinking (EFT), have decreased delay discounting and demand for alcohol. Rate dependence, the relationship between a baseline rate and change in that rate after an intervention, has been evidenced as a marker of efficacious substance use treatment, but whether narrative interventions have rate-dependent effects needs to be better understood. We investigated the effects of narrative interventions on delay discounting and hypothetical demand for alcohol in this longitudinal, online study. Individuals (n= 696) reporting high- or low-risk alcohol use were recruited for a longitudinal 3-week survey via Amazon Mechanical Turk. Delay discounting and alcohol demand breakpoint were assessed at baseline. Individuals returned at weeks 2 and 3 and were randomized into the EFT or scarcity narrative interventions and again completed the delay discounting tasks and alcohol breakpoint task. Oldham's correlation was used to explore the rate-dependent effects of narrative interventions. Study attrition as a function of delay discounting was assessed. Episodic future thinking significantly decreased, while scarcity significantly increased delay discounting relative to baseline. No effects of EFT or scarcity on the alcohol demand breakpoint were observed. Significant rate-dependent effects were observed for both narrative intervention types. Higher delay discounting rates were associated with a greater likelihood of attrition from the study. The evidence of a rate-dependent effect of EFT on delay discounting rates offers a more nuanced, mechanistic understanding of this novel therapeutic intervention and can allow more precise treatment targeting by demonstrating who is likely to receive the most benefit from it.

Moderate Stability among Delay, Probability, and Effort Discounting in Humans

The stability of delay discounting across time has been well-established. However, limited research has examined the stability of probability discounting, and no studies of the stability of effort discounting are available. The present study assessed the steady-state characteristics of delay, probability, and effort discounting tasks across time with hypothetical rewards in humans, as well as whether response characteristics suggested a common discounting equation. Participants completed delay, probability, and effort discounting tasks on three occasions. We found moderate relative stability of delay and probability tasks, and similar evidence for absolute stability across time for all tasks. The interclass correlations coefficient showed some correspondence across time points and tasks, and higher levels of between subject variability, especially for the effort discounting task, suggesting trait level variables has a stronger influence on performance than state level variables. Performance on the delay and probability tasks were moderately correlated and similar mathematical functions fit choice patterns on both tasks (hyperbolic), suggesting that delay and probability discounting processes shared some common elements. Lower correlations and different function fits suggested that effort discounting involves more unique features.

Previous experience with delays affects delay discounting in animal model of ADHD

BackgroundADHD is a disorder where a common symptom is impulsive behaviour, a broad term associated with making sub-optimal choices. One frequently used method to investigate impulsive behaviour is delay discounting, which involves choosing between a small, immediate reinforcer and a delayed, larger one. Choosing the small immediate reinforcer is by itself, however, not sufficient for terming the choice impulsive, as all organisms eventually switch to choosing the small, immediate reinforcer when the delay to the larger reinforcer becomes long. This switch can be termed impulsive only when it occurs more frequently, or at shorter LL delays, than typically observed in normal controls. A poorly understood aspect is how choice is influenced by previous experience with delays. Using an animal model of Attention-Deficit/Hyperactivity Disorder, the Spontaneously Hypertensive Rat, we manipulated the order of exposure to delays in a delay discounting task. Following a preference test, the Ascending group experienced gradually increasing delays between choice and reinforcer while the Descending group were exposed to these delays in reverse order.ResultsThe results showed that the Descending group chose the small, immediate reinforcer over the larger delayed to a much larger extent than the Ascending group, and continued to do so even when the delay component was ultimately removed. Strain effects were found in the Ascending group, with SHRs switching to the small, immediate reinforcer earlier than controls as the delay to the larger reinforcer increased.ConclusionThe data suggests that delay discounting is affected by history of exposure to delayed consequences. When reinforcement contingencies are incrementally changed from having no response-reinforcer delay to a long delay, discounting of delayed consequences is gradual. However, a sudden change from no delay to a long delay, without intermediate training, results in a rapid switch to the small, immediate reinforcer option, and this behaviour is somewhat resilient to the shortening and eventual removal of the large reinforcer delay. The implication is that attempting to reduce already existing impulsive behaviour in children with ADHD will require gradual habituation and not sudden changes in reinforcement contingencies.

Beyond BMI: cardiometabolic measures as predictors of impulsivity and white matter changes in adolescents

Obesity is characterized by cardiometabolic and neurocognitive changes. However, how these two factors relate to each other in this population is unknown. We tested the association that cardiometabolic measures may have with impulse behaviors and white matter microstructure in adolescents with and without an excess weight. One hundred and eight adolescents (43 normal-weight and 65 overweight/obesity; 11–19 years old) were medically and psychologically (Temperament Character Inventory Revised, Three-Factor Eating Questionnaire-R18, Conners’ Continuous Performance Test-II, Stroop Color and Word Test, Wisconsin Card Sorting Test, Kirby Delay Discounting Task) evaluated. A subsample of participants (n = 56) underwent a brain magnetic resonance imaging acquisition. In adolescents, higher triglycerides and having a body mass index indicative of overweight/obesity predicted a more impulsive performance in Conners’ Continuous Performance Test-II (higher commission errors). In addition, higher glucose and diastolic blood pressure values predicted increments in the Three-Factor Eating Questionnaire-R18 emotional eating scale. Neuroanatomically, cingulum fractional anisotropy showed a negative relationship with glycated hemoglobin. The evaluation of the neurocognitive differences associated with obesity, usually based on body mass index, should be complemented with cardiometabolic measures.

Valuation of future alcohol in cross-commodity delay discounting is associated with alcohol misuse/consequences.

Delay discounting (DD) refers to the reduction in reward value as a function of its delay, and individuals who misuse alcohol typically exhibit high rates of DD, which may reflect a general preference for immediate outcomes. This interpretation is based on studies utilizing single-commodity DD tasks where the same commodity is available immediately and following a delay. Cross-commodity DD tasks require individuals to choose between different commodities at varying delays and may provide the potential to further illuminate intertemporal preference associated with alcohol misuse. The present study examined associations between single-commodity and cross-commodity DD rates with alcohol use metrics among young adults. DD by young adults (N = 70, aged 19-24, 71% male, 80% White) who engage in hazardous drinking was examined using a fully parametric combination of immediate and delayed alcohol and money outcomes. We hypothesized that past 30-day alcohol use and alcohol-related negative consequences would be associated with preference for alcohol outcomes independent of whether alcohol was immediate or delayed. Results support the hypothesis, as past 30-day consumption and AUDIT scores were positively associated with rate of DD in the immediate alcohol versus delayed money task and negatively associated with rate of DD in the immediate money versus delayed alcohol task. Moreover, we found the immediate money versus delayed alcohol task provided unique explanatory power for individual alcohol use. The observed associations indicate that willingness to invest in future access to alcohol may be associated with elevated alcohol use and related consequences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impulsive choice in two different rat models of ADHD-Spontaneously hypertensive and Lphn3 knockout rats.

Impulsivity is a symptom of attention-deficit/hyperactivity disorder (ADHD) and variants in the Lphn3 (Adgrl3) gene (OMIM 616417) have been linked to ADHD. This project utilized a delay-discounting (DD) task to examine the impact of Lphn3 deletion in rats on impulsive choice. "Positive control" measures were also collected in spontaneously hypertensive rats (SHRs), another animal model of ADHD. For Experiment I, rats were given the option to press one lever for a delayed reward of 3 food pellets or the other lever for an immediate reward of 1 pellet. Impulsive choice was measured as the tendency to discount the larger, delayed reward. We hypothesized that impulsive choice would be greater in the SHR and Lphn3 knockout (KO) rats relative to their control strains - Wistar-Kyoto (WKY) and Lphn3 wildtype (WT) rats, respectively. The results did not completely support the hypothesis, as only the SHRs (but not the Lphn3 KO rats) demonstrated a decrease in the percent choice for the larger reward. Because subsequent trials did not begin until the end of the delay period regardless of which lever was selected, rats were required to wait for the next trial to start even if they picked the immediate lever. Experiment II examined whether the rate of reinforcement influenced impulsive choice by using a DD task that incorporated a 1 s inter-trial interval (ITI) immediately after delivery of either the immediate (1 pellet) or delayed (3 pellet) reinforcer. The results of Experiment II found no difference in the percent choice for the larger reward between Lphn3 KO and WT rats, demonstrating reinforcement rate did not influence impulsive choice in Lphn3 KO rats. Overall, there were impulsivity differences among the ADHD models, as SHRs exhibited deficits in impulsive choice, while the Lphn3 KO rats did not.

Neurobehavioral phenotypes of delay discounting and cognitive control in child attention-deficit/hyperactivity disorder and obesity: Shared or distinct?

Attention-deficit/hyperactivity disorder (ADHD) and obesity have been independently associated with deficient cognitive control (CC) and heightened preference for immediate reward. We aimed to identify specific shared and distinct neurobehavioral phenotypes of child obesity and ADHD by simultaneously measuring CC and preference for immediate reward in children with and without ADHD who varied in body weight. This case-control study included 323 8-12 year olds (ADHD n=215, typically developing (TD) screened for ADHD symptoms [TD] controls n=108) varying in body weight. Children completed a go/no-go task (assessing CC), as well as a classical money delay discounting (DD) task and novel experiential game time DD task (assessing preference for immediate over delayed rewards). For game time DD, there was a body mass index z-score (BMIz)*ADHD interaction, such that TD children with overweight/obesity showed game time DD levels that were greater than those of TD children without overweight/obesity and similar to those of children with ADHD. Only children with ADHD showed poorer CC compared to TD children, with no effects of body weight. Heightened game time DD with delays and rewards experienced in real-time may represent a neurobehavioral phenotype that is shared between ADHD and overweight/obesity in childhood, whereas deficient CC may be specific to children with ADHD.

Model-based experimental manipulation of probabilistic behavior in interpretable behavioral latent variable models.

Interpretable latent variable models that probabilistically link behavioral observations to an underlying latent process have increasingly been used to draw inferences on cognition from observed behavior. The latent process usually connects experimental variables to cognitive computation. While such models provide important insights into the latent processes generating behavior, one important aspect has often been overlooked. They may also be used to generate precise and falsifiable behavioral predictions as a function of the modeled experimental variables. In doing so, they pinpoint how experimental conditions must be designed to elicit desired behavior and generate adaptive experiments. These ideas are exemplified on the process of delay discounting (DD). After inferring DD models from behavior on a typical DD task, the models are leveraged to generate a second adaptive DD task. Experimental trials in this task are designed to elicit 9 graded behavioral discounting probabilities across participants. Models are then validated and contrasted to competing models in the field by assessing the ouf-of-sample prediction error. The proposed framework induces discounting probabilities on nine levels. In contrast to several alternative models, the applied model exhibits high validity as indicated by a comparably low prediction error. We also report evidence for inter-individual differences with respect to the most suitable models underlying behavior. Finally, we outline how to adapt the proposed method to the investigation of other cognitive processes including reinforcement learning. Inducing graded behavioral frequencies with the proposed framework may help to highly resolve the underlying cognitive construct and associated neuronal substrates.

Reward-related episodic future thinking and delayed gratification in children

Cuing adults to imagine their personal futures enhances prudent choice in delay discounting tasks. However, it has not been established that such cueing also reduces discounting in children. We assessed the effect of episodic future thinking (EFT) on delay of gratification in children using EFT cues specifically related to the rewards on offer. One hundred and thirty-nine 8–12-year-olds were assigned to one of three conditions: (i) EFT (imagine spending money in the future), (ii) Imagine Place (imagine being in a certain place), or (iii) No Cue. They were cued on each trial of two tasks: a delay discounting task with hypothetical monetary rewards and a real delay choice task involving choices between real rewards over real delays (coins that could be swapped for treats). In the delay discounting task, the Imagine Place group showed significantly higher discounting than the other two groups. In the real delay choice task, the Imagine Place group made significantly fewer delayed choices than the EFT group. However, the EFT group did not differ from the No Cue group in either task. The lack of a difference between the EFT and No Cue conditions supports previous findings suggesting children struggle to benefit from EFT cues. Poorer performance of the Imagine Place group suggests that cued imagination is cognitively taxing for children, using up cognitive resources required to delay gratification.

Effect of psilocybin on decision-making and motivation in the healthy rat

Psilocybin and its active metabolite psilocin are hallucinogenic serotonergic agonists with high affinity for several serotonin receptors. In addition to underlying the hallucinogenic effects of these compounds, serotonin receptor activation also has important effects on decision-making and goal-directed behaviors. The impact of psilocybin and psilocin on these cognitive systems, however, remains unclear. This study investigated the effects of psilocybin treatment on decision-making and motivation in healthy male and female rats. We compared probability and delay discounting performance of psilocybin treated (1 mg/kg) to vehicle rats (n = 10/sex/group), and further assessed motivation in each group using a progressive ratio task. We also confirmed drug action by assessing head twitch responses after psilocybin treatment (1 mg/kg). Results from this study demonstrated that exposure to 1 mg/kg psilocybin did not affect decision-making in the probability and delay discounting tasks and did not reduce response rates in the progressive ratio task. However, psilocybin treatment did cause the expected increase in head twitch responses in both male and female rats, demonstrating that the drug was delivered at a pharmacologically relevant dosage. Combined, these results suggest that psilocybin may not impair or improve decision-making and motivation. Considering recent interest in psilocybin as a potential fast-acting therapeutic for a variety of mental health disorders, our findings also suggest the therapeutic effects of this drug may not be mediated by changes to the brain systems underlying reward and decision-making. Finally, these results may have important implications regarding the relative safety of this compound, suggesting that widespread cognitive impairments may not be seen in subjects, even after chronic treatment.

Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up.

Earlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU. We characterized neural and behavioral factors associated with reward-sensitivity and risk-taking in substance-naïve adolescents (N = 70; 11.1-14.0 years), examining whether these factors differed as a function of subsequent SU initiation at 18- and 36-months follow-up. Adolescents completed a reward-related decision-making task while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk [Drug Use Screening Inventory, Revised (DUSI-R)] were collected. These metrics were compared for youth who did [Substance Initiators (SI); n = 27] and did not [Substance Non-initiators (SN); n = 43] initiate SU at follow-up. While SI and SN youth showed similar task-based risk-taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. Groups displayed similar discounting behavior. SI participants scored higher on the DUSI-R and the BAS sub-scale. Activation patterns in the insula and anterior cingulate cortex may serve as a biomarker for earlier SU initiation. Importantly, these brain regions are implicated in the development and experience of SUDs, suggesting differences in these regions prior to substance exposure.

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 neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making

Why do people discount future rewards? Multiple theories in psychology argue that one reason is that future events are imagined less vividly than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the vividness of prospective thought, using an fMRI dataset where the vividness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay-discounting task, to show that neural measures of vividness decline as rewards are delayed farther into the future.

A Touchscreen Device for Behavioral Testing in Pigs.

Pigs are becoming more common research models due to their utility in studying neurological conditions such as traumatic brain injury, Alzheimer’s disease, and Huntington’s Disease. However, behavioral tasks often require a large apparatus and are not automated, which may disinterest researchers in using important functional measures. To address this, we developed a touchscreen that pigs could be trained on for behavioral testing. A rack-mounted touchscreen monitor was placed in an enclosed, weighted audio rack. A pellet dispenser was operated by a radio frequency transceiver to deliver fruit-flavored sugar pellets from across the testing room. Programs were custom written in Python and executed on a microcomputer. A behavioral shaping program was designed to train pigs to interact with the screen and setup responses for future tasks. Pigs rapidly learned to interact with the screen. To demonstrate efficacy in more complex behavior, two pigs were trained on a delay discounting tasks and two pigs on a color discrimination task. The device held up to repeated testing of large pigs and could be adjusted to the height of minipigs. The device can be easily recreated and constructed at a relatively low cost. Research topics ranging from brain injury to pharmacology to vision could benefit from behavioral tasks designed to specifically interrogate relevant function. More work will be needed to develop tests which are of specific relevance to these disciplines.

Differences in attentional bias to smoking-related, affective, and sensation-seeking cues between smokers and non-smokers: an eye-tracking study.

One of the behavioural features of tobacco use disorder is the presence of attentional bias (AB) to smoking-related stimuli. However, much of the research investigating these associations have been limited to the use of reaction-based indices. We aimed to investigate differences in AB to smoking, affective, and sensation-seeking cues in smokers and non-smokers using novel, free-viewing, eye-tracking technology. Secondary aims included investigating impulsivity-by-group interaction effects on AB to sensation-seeking cues. Participants were either otherwise-healthy smokers of at least 8 cigarettes per day or otherwise-healthy non-smokers (< 100 cigarettes in their lifetime and no smoking in the past year). AB was measured using a free-viewing, eye-tracking system. Participants were presented a series of slides divided into 3 themes: smoking, affective, and sensation-seeking. Each slide contained 4 images (1 theme-related, 1 neutral, 2 competitive). Primary outcome measure was the difference in the proportion of time spent viewing the theme-related cue to neutral cue. Impulsivity was measured using a monetary delayed discounting task. The sample consisted of 50 smokers (41 ± 12years old) and 50 age- and sex-matched non-smokers (40 ± 14years old). Smokers spent over 2 times longer looking at smoking-related images than non-smokers (F = 25.50, p < 0.001). As well, greater impulsivity was significantly associated with increased AB to sensation-seeking cues (R2 = 0.059, F = 2.98, p = 0.04) in smokers but not non-smokers. No differences were found on AB to affective cues. The eye-tracking procedure is a sensitive tool for assessing AB in smokers compared to non-smokers to both smoking and sensation-seeking cues.

Developmental trajectories of delay discounting from childhood to young adulthood: longitudinal associations and test-retest reliability

Delay discounting (DD) indexes an individual’s preference for smaller immediate rewards over larger delayed rewards, and is considered a form of cognitive impulsivity. Cross-sectional studies have demonstrated that DD peaks in adolescence; longitudinal studies are needed to validate this putative developmental trend, and to determine whether DD assesses a temporary state, or reflects a more stable behavioral trait. In this study, 140 individuals aged 9–23 completed a delay discounting (DD) task and cognitive battery at baseline and every-two years thereafter, yielding five assessments over approximately 10 years. Models fit with the inverse effect of age best approximated the longitudinal trajectory of two DD measures, hyperbolic discounting (log[k]) and area under the indifference-point curve (AUC). Discounting of future rewards increased rapidly from childhood to adolescence and appeared to plateau in late adolescence for both models of DD. Participants with greater verbal intelligence and working memory displayed reduced DD across the duration of the study, suggesting a functional interrelationship between these domains and DD from early adolescence to adulthood. Furthermore, AUC demonstrated good to excellent reliability across assessment points that was superior to log(k), with both measures demonstrating acceptable stability once participants reached late adolescence. The developmental trajectories of DD we observed from childhood through young adulthood suggest that DD may index cognitive control more than reward sensitivity, and that despite modest developmental changes with maturation, AUC may be conceptualized as a trait variable related to cognitive control vs impulsivity.

The Effects of Citalopram and Thalamic Dopamine D2/3 Receptor Availability on Decision-Making and Loss Aversion in Alcohol Dependence.

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients who misuse alcohol, especially in the context of comorbid depressive symptoms. Deficits in impulse control and decision-making are linked to routine alcohol consumption and alcohol dependence. The goal of this study was to determine the effects of a single dose of citalopram on measures of impulsivity, decision-making, and/or brain dopamine receptor availability in alcohol-dependent individuals. A double-blind, placebo-controlled, within-subject, outpatient study was conducted with active alcohol-dependent (DSM-IV-TR criteria) participants (n = 12) and matched healthy controls (n = 13). Serial doses of both citalopram (40 mg) and saline were administered intravenously before laboratory tests of decision-making (Balloon Analogue Risk Task, delay discounting task, and Loss Aversion Gambling Task) and positron emission tomography with [18F]-fallypride to measure dopamine D2/3 receptor availability, separated by at least one week. Alcohol-dependent participants demonstrated greater loss aversion than healthy controls, but there were no group differences in risk taking on the Balloon Analogue Risk Task. Citalopram increased delay discounting across groups, with no group difference in the effect. There were no effects of citalopram on risk taking on the Balloon Analogue Risk Task. PET showed a negative correlation between thalamic dopamine D2/3 receptor availability and loss aversion across groups. The effect of citalopram to decrease the valuation of monetary reward as a function of delay raises the possibility that SSRIs can influence risky decision-making in clinical populations. In addition, these results suggest that altered thalamic dopamine signaling may play an important role in disproportionately valuing losses in patients with Alcohol Use Disorder. This trial is registered under ClinicalTrials.gov registration NCT01657760.

Contrasting effects of DOI and lisuride on impulsive decision-making in delay discounting task.

The 5-HT2A receptor is the major target of classic hallucinogens. Both DOI (2,5-dimethoxy-4-iodoamphetamine) and lisuride act at 5-HT2A receptors, and lisuride shares comparable affinity with DOI and acts as a partial agonist at 5-HT2A receptors. However, not like DOI, lisuride lacks hallucinogenic properties. Impulsive decision-making refers to the preference for an immediate small reinforcer (SR) over a delayed large reinforcer (LR). The current study aims to compare the effects of DOI and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs. Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percentage of choice for the LR in delay discounting task (DDT). Delay to the LR changed in an ascending order (0, 4, 8, 16, and 32s) across one session. DOI (0.5 and 1.0mg/kg) increased impulsive decision-making, and the effects of DOI (1.0mg/kg) were blocked by the 5-HT2A receptor antagonist ketanserin (1.0mg/kg) rather than the 5-HT2C receptor antagonist SB-242084 (1.0mg/kg). Contrarily, lisuride (0.1, 0.3, and 0.5mg/kg) decreased impulsive decision-making. The effects of lisuride (0.3mg/kg) were not antagonized by ketanserin (1.0mg/kg), selective 5-HT1A antagonist WAY-100635 (1.0mg/kg), or selective dopamine D4 receptor antagonist L-745870 (1.0mg/kg) but were attenuated by the selective dopamine D2/D3 receptor antagonist tiapride (40mg/kg). DOI and lisuride have contrasting effects on impulsive decision-making via distinct receptors. DOI-induced increase of impulsivity is mediated by the 5-HT2A receptor, while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.