Effects of acute and chronic administration of diazepam on delay discounting in Lewis and Fischer 344 rats

Impulsive choice is often examined using a delay-discounting procedure, where there is a choice between two reinforcers of different magnitudes presented at varying delays. Individual discounting rates can be influenced by many factors including strain differences and drug effects. Lewis (LEW) and Fischer 344 (F344) rats have behavioral and neurochemical differences relevant to delay discounting and were used to examine effects of acute and chronic administration of diazepam on impulsive choice. Consistent with the previous literature, larger-reinforcer choice decreased as a function of increasing delays for all rats, and steeper discounting functions were obtained for LEW relative to F344 rats. Acute and chronic administration of diazepam resulted in differential effects between rat strains and sometimes between subjects within the same rat strain. Overall, larger-reinforcer choice remained unchanged across multiple phases of the experiment for LEW rats. For F344 rats, larger-reinforcer choice increased following the acute administration of smaller doses of diazepam and decreased following the acute administration of the largest dose tested. Decreases in larger-reinforcer choice occurred for F344 rats during chronic and postchronic administration and persisted throughout a nondrug return-to-baseline phase. These results suggest potential directions for future investigation of environmental, genetic, and neurochemical variables involved in delay discounting.     

Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats

Rates of delay discounting (impulsive choice) have been shown to vary among individuals, particularly people who abuse drugs relative to those who do not, but factors that may contribute to these differences have not been identified. To explore a role for possible genetic and neurochemical determinants, Lewis (n = 8) and Fischer 344 (n = 8) rats were allowed to choose between one food pellet delivered immediately and three food pellets delivered after increasing delays. The delays to the large reinforcer (0, 10, 20, 40, 60 s) were increased across five blocks of trials in daily experimental sessions. For both groups of rats, choice for the larger reinforcer decreased as the delay to presentation increased. However, the Lewis rats were more likely to choose the smaller, immediate reinforcer earlier in the session, i.e., at shorter large-reinforcer delays, than the Fisher 344 rats. This difference in choice was statistically significant. Repeated administration of 3.0 mg/kg, i.p. clomipramine (mean of last five sessions) did not significantly alter choice, relative to baseline, for either strain. The present findings suggest that differences in delay discounting/impulsive choice may involve genetic, e.g., neurochemical, differences.     

Spontaneous withdrawal in opiate-dependent Fischer 344, Lewis and Sprague-Dawley rats

The Lewis (LEW) and Fischer 344 (F344) inbred rat strains react differentially to acute morphine administration for a variety of behavioral and neurochemical measures. Investigations into effects of chronic morphine are less common, and investigations assessing dependence have been limited to those utilizing antagonist-precipitated withdrawal. The present experiment extended these assessments by examining spontaneous withdrawal in the LEW and F344 strains. In this preparation, males of the LEW, F344 and the outbred Sprague-Dawley (SD) strain were made dependent on morphine. Following this, opiate administration was terminated and animals were examined for spontaneous withdrawal by the acquisition of a withdrawal-associated taste aversion, changes in body weight loss and the display of several behaviors characteristic of opiate withdrawal. Although all morphine-treated subjects decreased body weight and avoided consumption of the withdrawal-associated solution, indicating successful induction of dependence, no difference between the strains emerged in these indices of withdrawal severity. The only strain difference to appear in the behavioral indicators of withdrawal was with diarrhea (LEW > F344). That the strains differ in acute reactivity to opioids, but not in the overall severity of withdrawal, was discussed in relation to the need to examine the relationship between neurochemical and behavioral data in a variety of neural systems and behavioral endpoints.     

Central neurotensin receptor activation produces differential behavioral responses in Fischer and Lewis rats

Rationale Lewis (LEW) and Fischer (F344) rats exhibit marked differences in appetitive and consummatory responses to numerous drugs, including psychostimulants. Neurotensin (NT) produces psychostimulant-like actions, which sensitize with repeated exposure, and neuroleptic-like actions; effects that are dependent on the site of microinjection. The aim of the present experiments was to assess the behavioral sensitivity of these two strains of rats to NT receptor activation. Methods In expt 1, locomotor activity was assessed on alternate days following an ICV injection of NT, [d-Tyr¹¹]neurotensin (d-NT; 18 nmol/10 μl), or vehicle (days 1, 3, 5, and 7) in independent groups of LEW and F344 rats. On day 14, locomotor activity was assessed in all rats following an injection of d-amphetamine (1 mg/kg, IP). In expt 2, activity was assessed following injection into the ventral tegmental area of NT, or d-NT, (2.5 μg/hemisphere) or into the nucleus accumbens (2.5 and 5.0 μg/hemisphere). Results Repeated ICV injections of NT, or d-NT, produced differential behavioral effects in the two strains of rats on days 1–7; activity was initially suppressed in LEW, but less so in F344 rats, following NT. In F344, but not in LEW rats, d-NT produced a significant increase in activity. Neurotensin and d-NT sensitized LEW rats to amphetamine-induced ambulatory and non-ambulatory activity. Except for vertical activity, this effect was weaker or in the opposite direction in F344 rats. When injected into the ventral tegmental area, NT produced an increase in locomotor activity in both strains, an effect that was greater in F344 than LEW rats with d-NT. In the nucleus accumbens, NT marginally decreased activity in both strains, while d-NT produced a significant increase in F344 but not in LEW rats. Conclusions These results provide empirical evidence that endogenous NT neurotransmission within limbic circuitry differs in F344 and LEW rats.     

Impulsive choice, as measured in a delay discounting paradigm, remains stable after chronic heroin administration

Heroin addicts display poorer impulse control than non-addicts, however it is not known if high impulsivity is a function of chronic heroin intake or a pre-disposing vulnerability for heroin addiction. Using animal models, relatively few studies have examined changes in impulsive choice as a function of chronic drug. The objective of this study was to measure alterations in impulsive choice through a delay discounting paradigm, as a function of chronic heroin administration. Animals were trained on a series of delay discounting sessions. Each session contained 5 blocks of trials. Blocks started with 2 forced, followed by 6 free choice trials. Pressing one lever resulted in the delivery of a small immediate (1 food pellet) reward and another lever in a large delayed (5 pellets) reward. Sessions consisted of the 3 ascending delay sequences in seconds. On the terminal sequence (0, 10, 20, 40, and 60 s) animals exhibited a reversal of reward choice pattern of responding that allowed for the calculation of an indifference point (IP). After animals showed stable IPs they were treated with either heroin or saline for 12 days. Three days after the last injection animals were again placed in operant chambers and experienced the terminal delay discounting sequence at which time IPs were reassessed. Heroin-treated animals exhibited significant progressive increases in locomotor activity. Groups did not differ in IPs or performance across delay conditions during either before or after chronic treatment periods. These results indicate that chronic heroin intake does not impact later impulsive responding for natural (food) reward.     

A within-subject analysis of d-amphetamine exposure on delay discounting in rats

Studies concerning the relation between stimulant drug exposure and subsequent delay discounting (impulsive choice) have resulted in mixed findings that could be related to the type of stimulant drug exposure or the use of between-subject comparisons. The purpose of the present study was to examine effects of prior d-amphetamine exposure on subsequent delay discounting using a within-subject assessment. Two groups of rats were trained under a discrete-trials choice procedure until delay discounting was stable. One group of rats then received repeated administration of 3.0 mg/kg d-amphetamine in their home cage for 14 consecutive days, while the other group received saline. After a three-week drug-free period, delay discounting was reassessed. No significant differences in area under the curve within (before or after drug exposure) or between (saline or d-amphetamine) groups were found. Thus, delay discounting was not systematically affected following termination of repeated 3.0 mg/kg d-amphetamine exposure in the present experimental arrangement. The current results, coupled with past research, indicate that there may be a distinction between cocaine exposure and d-amphetamine exposure on subsequent delay discounting; however, within-subject comparisons of cocaine exposure on delay discounting are warranted.     

Effects of acute and chronic methylphenidate on delay discounting

Methylphenidate (MPH) is one of the most common therapeutics used for the treatment of attention-deficit/hyperactivity disorder (ADHD), which consists of symptoms of inattention, and/or impulsivity and hyperactivity. Acute administration of MPH has been found to decrease impulsive choice in both humans and nonhuman animals, however, little is known about potential long-term changes in impulsive choice due to chronic administration of MPH. In the present experiment, effects of acute and chronic MPH (1.0-10.0 mg/kg) were assessed on impulsive choice in the adult male Spontaneously Hypertensive Rat (SHR) to determine the extent of behavioral changes after chronic MPH exposure. Subjects chose between an immediate single food pellet and three food pellets delivered after a delay that increased within session (0 to 16 s). At relatively higher doses during acute and chronic administration, choice maintained by the larger reinforcer was disrupted when there was no delay to either outcome, suggesting that MPH may be affecting stimulus control under the current delay-discounting task. When this disruption was not observed, however, MPH effects were selective in that only one intermediate dose (3.0 mg/kg) decreased mean impulsive choice at one delay (8 s) following acute administration. The same effect was observed following chronic MPH administration except that the dose was higher (5.6 mg/kg) and the delay was shorter (4 s). Chronic administration of MPH did not show any negative indicators (e.g., an increase in impulsive choice) when administration was discontinued.     

Neuromodulation of delay discounting,the reflection effect,and cigarette consumption

Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices. Greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n = 47) and nonsmokers (n = 19) underwent three counterbalanced sessions of HF rTMS (20 Hz, 10 Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F_[3,250] = 4.46, p < .01), but increased discounting of monetary losses (F_[3,246] = 4.30, p < .01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive–behavioral interventions.     

High impulsivity in rats predicts amphetamine conditioned place preference

Stimulants such as d-amphetamine (AMPH) are used commonly to treat attention-deficit hyperactivity disorder (ADHD), but concerns have been raised regarding the use of AMPH due to its reinforcing and potentially addictive properties. The current study examined if individual differences in impulsive choice predict AMPH-induced hyperactivity and conditioned place preference (CPP). Rats were first tested in delay discounting using an adjusting delay procedure to measure impulsive choice and then were subsequently tested for AMPH CPP. High impulsive (HiI) and low impulsive (LoI) rats were conditioned across four sessions with 0.1, 0.5, or 1.5 mg/kg of AMPH. AMPH increased locomotor activity for HiI and LoI rats following 0.5 mg/kg but failed to increase activity following 0.1 and 1.5 mg/kg. CPP was established for HiI rats with both 0.5 and 1.5 mg/kg of AMPH, whereas LoI rats did not develop CPP following any dose of AMPH; HiI and LoI groups differed significantly following 0.5 mg/kg of AMPH. These results indicate that HiI rats are more sensitive to the rewarding effects of AMPH compared to LoI rats, which is consistent with research showing that high impulsive individuals may be more vulnerable to stimulant abuse.     

Assessment of the aversive effects of peripheral mu opioid receptor agonism in Fischer 344 and Lewis rats

The Fischer 344 (F344) and Lewis (LEW) inbred rat strains differ on a host of biochemical, neuroanatomical, immunological and behavioral endpoints. One behavioral difference of interest is their differential reactivity to the aversive effects of morphine as indexed by the conditioned taste aversion preparation (aversions acquired by F344 rats are significantly greater than those acquired by the LEW strain). This differential effect appears to be specific to opioids that work primarily on the mu opioid receptor. Given that morphine works systemically, it is unknown whether these differential effects in F344 and LEW animals are centrally or peripherally mediated. To address this issue, the present study investigated the ability of the peripherally acting mu preferring opioid agonist loperamide to induce differential taste aversions in F344 and LEW animals. Both F344 and LEW animals acquired dose-dependent taste aversions to the loperamide-associated solution with no difference between them. Additionally, control animals initially injected with vehicle during aversion training with loperamide and subsequently conditioned with morphine displayed the typical aversive profile to morphine (F344 > LEW). Although the basis for the present data is unknown, their relation to morphine-induced taste aversions and the role of the interaction of stimulus effects of drugs that produce differential abuse liability were discussed.     

Effects of olanzapine on extracellular concentrations and tissue content of neurotensin in rat brain regions

We have previously shown that both the psychostimulant d-amphetamine and the antipsychotics haloperidol and risperidone affect extracellular concentrations and tissue content of neurotensin (NT) in distinct brain regions. This study investigated the effects of acute olanzapine (1, 5 mg/kg, s.c.) on extracellular NT-like immunoreactivity (− LI) concentrations in the ventral striatum (vSTR) and the medial prefrontal cortex (mPFC), and the effects of acute d-amphetamine (1.5 mg/kg, s.c.) on extracellular NT-LI in these brain regions after a 30-day olanzapine (15 mg/kg, p.o.) administration in rats. The effects of a 30-day olanzapine (3, 15 mg/kg, p.o.) administration and d-amphetamine (1.5 mg/kg, s.c.) coadministration during either the last day (acute) or the last 8 days (chronic) on NT-LI tissue content in distinct rat brain regions were also studied. Acute olanzapine increased extracellular NT-LI, in both the vSTR and the mPFC. Chronic olanzapine increased and decreased basal extracellular NT-LI in the vSTR and the mPFC, respectively, and abolished the stimulatory effects of acute d-amphetamine on extracellular NT-LI in these brain regions. Chronic olanzapine as well as acute and chronic d-amphetamine affected NT-LI tissue content in a brain region-dependent manner. Chronic olanzapine prevented the effects of acute and chronic d-amphetamine on NT-LI tissue content in certain brain regions. The fact that olanzapine and d-amphetamine affected extracellular NT-LI in the vSTR and mPFC as well as NT-LI tissue content in distinct brain regions further supports the notion that NT plays a role in the therapeutic actions of antipsychotic drugs and possibly also in the pathophysiology of schizophrenia.     

Acute nicotine reduces and repeated nicotine increases spontaneous activity in male and female Lewis rats

The Lewis (LEW) strain of rat appears more sensitive to nicotine than other strains in self-administration, conditioned place preference, and drug discrimination behavioral studies. The present study sought to further evaluate the behavioral effects of chronic nicotine treatment in the LEW strain by assessing spontaneous activity, which has consistently revealed sensitization to chronic nicotine administration in Sprague Dawley (SD) rats. High active and low active male and female LEW rats (N = 8 per group) were treated twice daily with either nicotine (0.4 mg/kg, sc) or vehicle for 14 consecutive days. Regardless of baseline activity level or sex, spontaneous activity was significantly decreased, compared to saline-treated rats, after a single nicotine injection. However, spontaneous activity increased in both low- and high-activity rats (both sexes) over the two weeks of nicotine administration to levels that were significantly higher than saline-treated rats. Based on these findings, acute and chronic nicotine administration had greater suppressive and enhancing effects on spontaneous activity in LEW rats compared to other strains of rats previously studied. These results further clarify the behavioral sensitivity of the LEW strain of rat to nicotine exposure and lend credence to the role of genetics in the individual susceptibility to nicotine dependence.     

Caffeine-induced taste aversions in Lewis and Fischer rat strains: differential sensitivity to the aversive effects of drugs

Lewis (LEW) and Fischer 344 (F344) rat strains have been reported to differ in the aversive effects induced by a number of drugs. The present studies extended this previous work and examined the ability of caffeine to induce taste aversions in the two strains. Specifically, LEW and F344 rats were given access to saccharin and injected with varying doses of caffeine (0, 0.32, 1.0 and 3.2 mg/kg—Experiment 1; 0, 10, 18 and 32 mg/kg—Experiment 2). Additionally, the effects of caffeine on locomotor activity were examined in Experiment 2. At low doses (Experiment 1), caffeine failed to induce taste aversions in either strain. At higher doses (Experiment 2), aversions were induced that were strain dependent. Specifically, caffeine induced taste aversions in both strains at 32 mg/kg, while 18 mg/kg caffeine was effective in inducing aversions only in the LEW strain. Caffeine increased activity in both strains with no strain difference. This demonstration adds to the growing list of drugs on which the LEW and F344 strains differ in relation to their affective properties. Given that drug use and abuse are a function of the balance of the rewarding and aversive effects of drugs, understanding such strain differences may provide insight into the biological (and genetic) factors impacting abuse vulnerability.     

Naloxone-precipitated conditioned taste aversions in morphine-dependent Fischer (F344) and Lewis rat strains

The Fischer 344 (F344) and Lewis (LEW) rat strains are genetically divergent populations that are used to study the effects of and responses to drugs of abuse. In this context, LEW rats display faster acquisition of drug self-administration than F344 rats. Interestingly, these strains have also been reported to differ in their somatic responses to morphine withdrawal. To address possible strain differences in the affective response to withdrawal, the present study assessed the ability of naloxone-precipitated withdrawal from morphine to induce conditioned taste aversions in male F344 and LEW rats. Specifically, subjects from each of these strains were given chronic morphine to induce dependence and then given access to a novel saccharin solution followed by naloxone. These pairings were given every fourth day for a total of two conditioning trials after which subjects were given access to saccharin but without naloxone administration to assess extinction of the naloxone-induced aversion. Behavioral assays of withdrawal were also performed after each naloxone administration. Both F344 and LEW subjects acquired aversions to the naloxone-associated taste with no significant differences in the rate of acquisition of the aversions. Differences did appear during extinction with LEW animals extinguishing the taste aversion significantly faster than F344 animals. The data were discussed in terms of the relative strength of the affective responses during withdrawal and the role of such responses to drug use and abuse.     

Effects of cigarette smoking status on delay discounting in schizophrenia and healthy controls

Background

Delay discounting is a measure of future-oriented decision-making and impulsivity. Cigarette smoking is associated with rapid discounting of the value of delayed outcomes. In schizophrenia, however, cigarette smoking improves certain neurocognitive impairments associated with the disorder which may explain the high smoking rates in this population. This study examined the relationship between cigarette smoking and delay discounting in schizophrenia and control participants.

Methods

A total of N = 130 participants, including those with schizophrenia (n = 68) and healthy controls (n = 62) were assessed on the Kirby Delay Discounting Task and compared across smoking status (smokers; non-smokers) and smoking history (current, former; never smokers).

Results

Smokers exhibited higher discounting rates (i.e., were more impulsive) than non-smokers of the same diagnostic group. Current and former smokers with schizophrenia exhibited similar and significantly higher discounting rates than never smokers, suggesting that in schizophrenia delay discounting is a trait-dependent phenomenon independent of current cigarette smoking. Consistent with previous studies, there was a trend for higher discounting rates in control current smokers compared to control former and never smokers.

Conclusions

Smokers with and without schizophrenia have higher rates of delay discounting than non-smokers. However, in schizophrenia, rapid delay discounting appears to be a trait associated with having ever been a smoker (i.e., current and former smoking).     

Delay discounting and impulsivity traits in young and older gambling disorder patients

BackgroundImpulsivity is understood to be a multidimensional construct involving aspects such as impulsive choice and impulsive traits. Delay discounting, the tendency to place greater value in immediate rewards over larger, long-term rewards, has been associated with maladaptive choices in gambling disorder (GD). Delay discounting is known to evolve with age; though no study to date has evaluated the interactions between impulsivity, GD severity and age in treatment-seeking patients.ObjectivesWe aimed to examine whether associations between delay discounting and impulsivity traits differed between younger and older-aged GD patients. Secondly, we sought to untangle the mediating role of impulsivity in determining gambling behavior in these two age groups.MethodsGD patients (N = 335) were evaluated using the UPPS-P Impulsive Behavior Scale and a delay discounting task. Structural Equation Modeling (SEM) was used to explore associations between impulsivity measures and gambling severity in young (18–30 years) and old (31–70) GD patients.ResultsNo differences in delay discounting were found between young and old GD patients. Significant correlations between delay discounting and urgency levels (the tendency to act rashly under emotional states) were identified only in the young GD group. Path analyses also revealed both positive and negative urgency to be a mediator of GD severity levels in young GD patients.Discussion and conclusionsSignificant associations between impulsive choice and positive urgency are only present in young gamblers, suggesting that positive urgency influence choice behavior to a greater degree at younger ages. Implications for targeted interventions are discussed.     

Impact of strain and d-amphetamine on impulsivity (delay discounting) in inbred mice

Rationale Many studies have shown that human drug abusers are more impulsive than nonusers, but the mechanisms underlying this difference are unknown. C57BL/6J (B6) and DBA/2J (D2) mouse strains differ in sensitivity to the associative effects and in self-administration of several drugs of abuse.Objective To determine whether these strains exhibit differences in impulsivity that might correspond to the differences in phenotypes related to drug seeking.Methods We examined impulsive choice in drug-naive B6 and D2 mice using a delay discounting protocol (adjusting amount procedure, J Exp Anal Behav 67:353–366, 1997).Results Contrary to our initial expectations, we observed greater delay discounting (higher impulsivity) in D2 rather than in B6 mice. For both strains, discounting was enhanced by 0.80 and 1.20 mg/kg (i.p.) d-amphetamine relative to saline.Conclusions Data demonstrate the sensitivity of the procedure to strain differences and pharmacological manipulations. However, additional data are required to clarify the factors underlying this difference and how the delay discounting measure of impulsivity relates to phenotypic models of drug reinforcement and drug seeking.     

Trait differences in response to chronic nicotine and nicotine withdrawal in rats

Introduction

Understanding an individual’s vulnerability to drug addiction has important implications for the development of effective personal treatment plans. Although theories acknowledge impulsive behaviour as a key component of drug addiction, little is known about the influence of trait impulsivity on an individual’s susceptibility to the effects of psychostimulants on impulsivity at critical phases of the addiction cycle.

Methods

This study investigated the short and longer-term effects of chronic nicotine administration on impulsive choice in rats selected for high (HI) and low impulsivity (LI) on a delay discounting task. Rats prepared with subcutaneously osmotic mini-pumps received either nicotine (3.16 mg/kg/day [freebase]) or saline for 7 days. Performance was assessed during chronic treatment, early and late withdrawal, and in response to acute nicotine challenges following prolonged abstinence.

Results

Chronic nicotine increased impulsive choice in LI but not HI animals. Spontaneous withdrawal was associated with a nicotine abstinence syndrome, the early stages of which were characterised by opposing effects on impulsive choice in HI and LI animals. A transient decrease in impulsivity was observed in HI animals whilst the LI group remained more impulsive for up to 1 week following drug termination. Following normalisation of behaviour, acute nicotine challenges (0.125, 0.25, 0.5 mg/kg, SC) markedly increased impulsive choice regardless of trait impulsivity and drug history.

Conclusion

The results indicate that only LI individuals are vulnerable to chronic drug- and withdrawal-induced impairments in self-control which may increase the likelihood of the transition to, and maintenance of, nicotine dependence.     

The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats

Rationale

Impulsive behavior is categorically differentiated between impulsive action, the inability to withhold from acting out a response, and impulsive choice, the greater preference for an immediate and smaller reward over a delayed but more advantageous reward. While the effects of N-methyl-d-aspartic acid (NMDA) receptor antagonists on impulsive action have been extensively characterized, there are very few and conflicting reports on the effects of this class of drugs on impulsive choice.

Objectives

Using a modified adjusting delay task, we investigated the effects of uncompetitive and competitive blockade of NMDA receptors on impulsive choice.

Methods

Male Wistar rats were trained in a modified adjusting delay task, which involved repeated choice between a low reinforcing solution delivered immediately and a highly reinforcing solution delivered after a variable delay. Rats were then administered either the NMDA receptor uncompetitive antagonists ketamine or memantine, or the competitive antagonists D-AP-5 or CGS 19755.

Results

Ketamine treatment dose-dependently increased impulsive choice, and this effect was selective for low-impulsive but not high-impulsive rats. Similarly, memantine treatment dose-dependently increased impulsive choice with a preferential effect for low-impulsive rats. While D-AP-5 treatment did not affect impulsive choice, CGS 19755 increased impulsivity, however, at the same doses at which it caused a marked response inhibition.

Conclusions

NMDA receptor uncompetitive, but not competitive, antagonists significantly increased impulsive choice, preferentially in low-impulsive rats. These findings demonstrate that the effects of NMDA receptor blockade on impulsive choice are not generalizable and depend on the specific mechanism of action of the antagonist used.