Elsevier

Behavioural Brain Research

Volume 321, 15 March 2017, Pages 130-136
Behavioural Brain Research

Research report
Effects of nucleus accumbens amphetamine administration on performance in a delay discounting task

https://doi.org/10.1016/j.bbr.2017.01.001Get rights and content

Highlights

  • Chronic cocaine can increase both impulsive choice and nucleus accumbens (NAc) dopamine (DA) release.

  • Thus, enhanced NAc DA release could mediate chronic cocaine-induced impulsive choice.

  • Intra-NAc amphetamine increased choice of large rewards in an ascending delay discounting task.

  • Intra-NAc amphetamine decreased choice of the large rewards in a descending delay discounting task.

  • NAc DA may be important for flexible decision making.

Abstract

Chronic administration of cocaine can cause pronounced and enduring cognitive alterations such as increases in impulsive choice. Chronic cocaine can also result in enhanced dopamine (DA) release in the nucleus accumbens (NAc) in response to reward-related cues. It is possible that this enhanced DA release in the NAc is a mechanism by which cocaine increases impulsive choice. To date, however, the specific role of DA in the NAc in impulsive choice is unclear. To begin to address this, rats received acute microinjections of the indirect DA agonist amphetamine directly into the NAc prior to testing in a delay discounting task in which rats chose between a small, immediate and a large, delayed food reward. When delays to the large reward increased within test sessions, amphetamine increased choice of the large reward. When delays decreased within test sessions, however, amphetamine decreased choice of the large reward. These findings suggest that, rather than specifically mediating impulsive choice, DA neurotransmission in the NAc is necessary for flexible adaptation of choice strategies in the presence of shifting reward contingencies. These results further indicate that enhancements in NAc DA release likely do not account for lasting increases in impulsive choice caused by chronic cocaine.

Introduction

Substance use disorders are associated with cognitive and neurobiological impairments that can persist long after cessation of substance use [1]. One facet of cognition that is severely impacted is intertemporal decision making. Substance users typically display an exaggerated preference for immediate rewards, such as substances themselves, over delayed, but more beneficial rewards, such as prolonged abstinence, health and employment. Such preference for smaller, sooner over larger, more delayed rewards, or “impulsive choice,” is commonly assessed with delay discounting procedures in which subjects choose between two options, one which yields a small immediate reward and the other which yields a large reward that is delivered after varying delays [2]. All subjects decrease their choice of large rewards as the delays to their delivery increase; however, chronic users of alcohol, cocaine, and opioids, among other substances, show a steeper decrease in preference for large, delayed rewards than nonusers (i.e., steeper delay discounting, or increased impulsive choice; [3], [4], [5]). Despite numerous demonstrations of this phenomenon, the mechanisms by which chronic substance, and particularly cocaine, use increases impulsive choice remain poorly elucidated.

Aside from cognitive deficits, another consequence of chronic cocaine, either passively or self-administered, is enhanced dopamine (DA) release in the nucleus accumbens (NAc) in response to rewards and reward-related stimuli [6], [7]. Studies in rodents have shown that this sensitized DA release is associated with increases in non-drug reward-directed behavior [8] as well as cocaine-dependent behaviors such as psychomotor sensitization [9]. Given the co-occurrence of increased impulsive choice and sensitized NAc DA release following chronic cocaine administration, changes in NAc DA release may be a mechanism by which cocaine could cause increased impulsive choice. Evidence for this hypothesis includes the fact that both sensitized NAc DA release and cocaine-induced increases in impulsive choice are long-lasting phenomena (they can persist for months if not longer) [7], [10]. Additionally, artificially augmented NAc DA release enhances other aspects of reward-directed behavior, such as Pavlovian-instrumental transfer [11], [12]. Berridge [13] proposed that enhancements in DA release in the NAc may augment the incentive salience attributed to smaller, more immediate rewards over larger, delayed rewards, thus biasing choice toward more immediate gratification. Indeed, human neuroimaging data show that greater activity in the NAc is associated with choice of smaller, more immediate over larger, delayed monetary rewards [14], possibly reflecting greater salience ascribed to the immediate rewards. Together, these lines of evidence suggest that enhanced DA activity in the NAc may play a causal role in increased impulsive choice caused by chronic cocaine, possibly by enhancing the salience of more immediate gratification.

To determine whether enhanced NAc DA release could account for increased impulsive choice observed following chronic cocaine administration, we microinjected the indirect DA agonist amphetamine acutely into the NAc of rats prior to testing in a delay discounting task. This manipulation has been shown to increase incentive salience attributed to reward cues [8] in a manner similar to that produced by chronic cocaine administration [15]. Further, acute (although not chronic) systemic amphetamine has been shown to alter impulsive choice in a rodent delay discounting task [16], [17], [18], [19], [20], [21], [22], [23]. However, the effects of amphetamine directly into the NAc on impulsive choice have yet to be tested. Based on previous work, we predicted that intra-NAc amphetamine would increase impulsive choice, and that this would be due to enhancement of the salience of the small, immediate reward.

Section snippets

Subjects

Male Long-Evans rats (n = 73; 70 days old upon arrival; Charles River Laboratories, Raleigh, NC) were individually housed in a temperature controlled vivarium and kept on a 12 h light/dark cycle. Rats received free access to food and water except as noted. During behavioral training, rats were maintained at 85% of their free-feeding weight, with target weights adjusted upward by 5 g/week to account for growth. All animal procedures were conducted in accordance with the University of Florida

Histology

Of the initial 48 rats in the ascending group, 13 were excluded due to illness or death during surgery and 20 were excluded due to cannula misplacements. In the descending group, 11 out of the initial 25 rats were excluded due to cannula misplacements. In this same group, three additional rats were excluded due to illness during the experiment. Locations of cannula placements for rats included in the study (ascending, n = 15; descending, n = 11) are depicted in Fig. 1.

Effects of intra-accumbens amphetamine on delay discounting task performance

Rats were trained in the delay

Discussion

Taken together, the data show that acute intra-NAc amphetamine administration affects delay discounting task performance, but that the direction of the effect depends upon the order in which the delays are presented. These findings are consistent with previous work demonstrating that the effects of systemic amphetamine may depend on several different factors, such as the parameters of the delay discounting task and baseline levels of impulsivity. For example, as with the current findings, Tanno

Acknowledgements

We thank the Drug Supply Program at NIDA for kindly providing D-amphetamine. Supported by a McKnight Brain Institute Fellowship and a Thomas H. Maren Fellowship (CAO), DA033074 (MRM), and DA024671 and DA036534 (BS).

References (54)

  • S.N. Pradhan et al.

    Comparative effects of nicotine and amphetamine on timing behavior in rats

    Neuropharmacology

    (1970)
  • H.M. Arnold

    Systemic and intra-accumbens administration of amphetamine differentially affects cortical acetylcholine release

    Neuroscience

    (2000)
  • A. Mattsson

    Cortical cholinergic deficiency enhances amphetamine-induced dopamine release in the accumbens but not striatum

    Exp. Neurol.

    (2007)
  • S. He et al.

    Long-term opiate effects on amphetamine-induced dopamine release in the nucleus accumbens core and conditioned place preference

    Pharmacol. Biochem. Behav.

    (2004)
  • H. de Wit

    Impulsivity as a determinant and consequence of drug use: a review of underlying processes

    Addict. Biol.

    (2009)
  • K.R. Hamilton

    Choice impulsivity: definitions, measurement issues, and clinical implications

    Pers. Disord.

    (2015)
  • K.N. Kirby et al.

    Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls

    J. Exp. Psychol. Gen.

    (1999)
  • R.E. Vuchinich et al.

    Hyperbolic temporal discounting in social drinkers and problem drinkers

    Exp. Clin. Psychopharmacol.

    (1998)
  • L.J. Vanderschuren et al.

    Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies

    Psychopharmacology (Berl.)

    (2000)
  • C.L. Wyvell et al.

    Intra-accumbens amphetamine increases the conditioned incentive salience of sucrose reward: enhancement of reward wanting without enhanced liking or response reinforcement

    J. Neurosci.

    (2000)
  • M.R. Mitchell et al.

    Cocaine and intertemporal decision making

  • S. Pecina et al.

    Dopamine or opioid stimulation of nucleus accumbens similarly amplify cue-triggered ‘wanting' for reward: entire core and medial shell mapped as substrates for PIT enhancement

    Eur. J. Neurosci.

    (2013)
  • J.R. Taylor et al.

    Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens

    Psychopharmacology (Berl.)

    (1984)
  • K.C. Berridge

    The debate over dopamine's role in reward: the case for incentive salience

    Psychopharmacology (Berl.)

    (2007)
  • S.M. McClure

    Separate neural systems value immediate and delayed monetary rewards

    Science

    (2004)
  • K.H. LeBlanc et al.

    Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats

    PLoS One

    (2013)
  • T. Tanno

    Effects of amphetamine and methylphenidate on delay discounting in rats: interactions with order of delay presentation

    Psychopharmacology (Berl.)

    (2014)
  • Cited by (23)

    • Contrasting effects of d-amphetamine and atomoxetine on measures of impulsive action and choice

      2021, Pharmacology Biochemistry and Behavior
      Citation Excerpt :

      This design was motivated by the reports of Tanno et al. (2013) and Orsini et al. (2017), who reported that the effect of AMP on discounting was dependent on delay sequence. Despite the differences of injection route (systemic: Tanno et al., 2013; intra-accumbens: Orsini et al., 2017), in each case the effect of AMP was dependent on delay order, with a reduction in discounting under ascending delays, and an increased discounting under descending delays. The current study mirrored those findings.

    • Effects of a high-fat diet on impulsive choice in rats

      2021, Physiology and Behavior
      Citation Excerpt :

      After the last washout day, rats were shaped and tested in a progressive ratio schedule of reinforcement task for six days. Detailed shaping procedures for the delay discounting task have been previously described [31,32,48,49]. Briefly, rats underwent one session of magazine training, in which a single food pellet (45 mg) was delivered every 100 ± 40 s over a 64 min session.

    View all citing articles on Scopus
    View full text