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Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task

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Abstract

Rationale

Repeated amphetamine (AMPH) exposure is known to cause long-term changes in AMPH-induced locomotor behavior (i.e., sensitization) that are associated with similarly long-lasting changes in brain function. It is not clear, however, if such exposure produces long-lasting changes in a cognitive behavior that, in humans, is hypothesized to contribute to addiction.

Objectives

To examine whether repeated AMPH exposure induces both locomotor sensitization and alters impulsive choice in a delay-discounting task.

Materials and methods

Adult, male Sprague–Dawley rats (n = 29) were pretreated with 3.0 mg/kg AMPH or saline every other day for 20 days and were then trained to lever press for small, immediately delivered food reinforcement or larger reinforcements delivered after delays. We subsequently assessed the effects of acute AMPH (0.1–2.0 mg/kg) on delay-discounting. Lastly, we tested for long-lasting effects of pretreatment by giving an AMPH challenge (3.0 mg/kg) 1 week after the final delay-discounting session.

Results

Repeated AMPH produced sensitization to the drug’s stereotypy-inducing effects but did not alter acquisition or baseline behavior in the delay-discounting task. Following acute AMPH, impulsive choice and other measures of delay-discounting were altered, but to a similar extent in both saline- and AMPH-pretreated groups. The AMPH challenge, given ∼3 months after the last pretreatment injection, revealed that sensitization was still evident.

Conclusions

Our results suggest that one behavioral consequence of repeated AMPH exposure—sensitization—does not overlap with another potential outcome—increased impulsivity. Furthermore, the neuroadaptations known to be associated with sensitization may be somewhat distinct from those that lead to changes in impulsive choice.

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References

  • Badiani A, Robinson TE (2004) Drug-induced neurobehavioral plasticity: the role of environmental context. Behav Pharmacol 15:327–339

    Article  PubMed  CAS  Google Scholar 

  • Barbelivien A, Billy E, Lazarus C, Kelche C, Majchrzak M (2008) Rats with different profiles of impulsive choice behavior exhibit differences in responses to caffeine and d-amphetamine and in medial prefrontal cortex 5-HT utilization. Behav Brain Res 187:273–283

    Article  PubMed  CAS  Google Scholar 

  • Bechara A (2005) Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nat Neurosci 8:1458–1463

    Article  PubMed  CAS  Google Scholar 

  • Belcher AM, O’Dell SJ, Marshall JF (2006) A sensitizing regimen of methamphetamine causes impairments in a novelty preference task of object recognition. Behav Brain Res 170:167–172

    Article  PubMed  CAS  Google Scholar 

  • Bisagno V, Ferguson D, Luine VN (2003) Chronic d-amphetamine induces sexually dimorphic effects on locomotion, recognition memory, and brain monoamines. Pharmacol Biochem Behav 74:859–867

    Article  PubMed  CAS  Google Scholar 

  • Briand LA, Robinson TE, Maren S (2005) Enhancement of auditory fear conditioning after housing in a complex environment is attenuated by prior treatment with amphetamine. Learn Mem 12:553–556

    Article  PubMed  Google Scholar 

  • Cardinal RN, Robbins TW, Everitt BJ (2000) The effects of d-amphetamine, chlordiazepoxide, alpha-flupenthixol and behavioural manipulations on choice of signalled and unsignalled delayed reinforcement in rats. Psychopharmacology (Berl) 152:362–375

    Article  CAS  Google Scholar 

  • Castner SA, Vosler PS, Goldman-Rakic PS (2005) Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex. Biol Psychiatry 57:743–751

    Article  PubMed  CAS  Google Scholar 

  • Coffey SF, Gudleski GD, Saladin ME, Brady KT (2003) Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals. Exp Clin Psychopharmacol 11:18–25

    Article  PubMed  Google Scholar 

  • Dalley JW, Theobald DE, Berry D, Milstein JA, Laane K, Everitt BJ, Robbins TW (2005) Cognitive sequelae of intravenous amphetamine self-administration in rats: evidence for selective effects on attentional performance. Neuropsychopharmacology 30:525–537

    Article  PubMed  CAS  Google Scholar 

  • Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE, Laane K, Pena Y, Murphy ER, Shah Y, Probst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron JC, Everitt BJ, Robbins TW (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315:1267–1270

    Article  PubMed  CAS  Google Scholar 

  • de Wit H, Enggasser JL, Richards JB (2002) Acute administration of d-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology 27:813–825

    Article  PubMed  Google Scholar 

  • Deller T, Sarter M (1998) Effects of repeated administration of amphetamine on behavioral vigilance: evidence for “sensitized” attentional impairments. Psychopharmacology (Berl) 137:410–414

    Article  CAS  Google Scholar 

  • Ersche KD, Clark L, London M, Robbins TW, Sahakian BJ (2006) Profile of executive and memory function associated with amphetamine and opiate dependence. Neuropsychopharmacology 31:1036–1047

    Article  PubMed  CAS  Google Scholar 

  • Ersche KD, Roiser JP, Robbins TW, Sahakian BJ (2008) Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacology (Berl) 197:421–431

    Article  CAS  Google Scholar 

  • Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146:348–361

    Article  CAS  Google Scholar 

  • Evenden JL, Ryan CN (1996) The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology (Berl) 128:161–170

    Article  CAS  Google Scholar 

  • Fletcher PJ, Tenn CC, Rizos Z, Lovic V, Kapur S (2005) Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (Berl) 183:190–200

    Article  CAS  Google Scholar 

  • Fletcher PJ, Tenn CC, Sinyard J, Rizos Z, Kapur S (2007) A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Neuropsychopharmacology 32:1122–1132

    Article  PubMed  CAS  Google Scholar 

  • Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652

    Article  PubMed  Google Scholar 

  • Gulley JM, Reed JL, Kuwajima M, Rebec GV (2004) Amphetamine-induced behavioral activation is associated with variable changes in basal ganglia output neurons recorded from awake, behaving rats. Brain Res 1012:108–118

    Article  PubMed  CAS  Google Scholar 

  • Heil SH, Johnson MW, Higgins ST, Bickel WK (2006) Delay discounting in currently using and currently abstinent cocaine-dependent outpatients and non-drug-using matched controls. Addict Behav 31:1290–1294

    Article  PubMed  Google Scholar 

  • Hoffman WF, Moore M, Templin R, McFarland B, Hitzemann RJ, Mitchell SH (2006) Neuropsychological function and delay discounting in methamphetamine-dependent individuals. Psychopharmacology (Berl) 188:162–170

    Article  CAS  Google Scholar 

  • Jentsch JD, Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl) 146:373–390

    Article  CAS  Google Scholar 

  • Khantzian EJ (1985) The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry 142:1259–1264

    PubMed  CAS  Google Scholar 

  • Kirby KN, Petry NM (2004) Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls. Addiction 99:461–471

    Article  PubMed  Google Scholar 

  • Klawans HL, Margolin DI (1975) Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Implications in psychosis and human movement disorders. Arch Gen Psychiatry 32:725–732

    PubMed  CAS  Google Scholar 

  • Kolb B, Gorny G, Li Y, Samaha AN, Robinson TE (2003) Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Proc Natl Acad Sci USA 100:10523–10528

    Article  PubMed  CAS  Google Scholar 

  • Kolta MG, Shreve P, De Souza V, Uretsky NJ (1985) Time course of the development of the enhanced behavioral and biochemical responses to amphetamine after pretreatment with amphetamine. Neuropharmacology 24:823–829

    Article  PubMed  CAS  Google Scholar 

  • Levin FR, Kleber HD (1995) Attention-deficit hyperactivity disorder and substance abuse: relationships and implications for treatment. Harv Rev Psychiatry 2:246–258

    Article  PubMed  CAS  Google Scholar 

  • Lu W, Wolf ME (1999) Repeated amphetamine administration alters AMPA receptor subunit expression in rat nucleus accumbens and medial prefrontal cortex. Synapse 32:119–131

    Article  PubMed  CAS  Google Scholar 

  • Lyvers M (2000) “Loss of control” in alcoholism and drug addiction: a neuroscientific interpretation. Exp Clin Psychopharmacol 8:225–249

    Article  PubMed  CAS  Google Scholar 

  • McKetin R, Mattick RP (1998) Attention and memory in illicit amphetamine users: comparison with non-drug-using controls. Drug Alcohol Depend 50:181–184

    Article  PubMed  CAS  Google Scholar 

  • Monterosso J, Ainslie G (1999) Beyond discounting: possible experimental models of impulse control. Psychopharmacology (Berl) 146:339–347

    Article  CAS  Google Scholar 

  • Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, London M, Everitt BJ, Robbins TW (2000) Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology 23:113–126

    Article  PubMed  CAS  Google Scholar 

  • Paine TA, Dringenberg HC, Olmstead MC (2003) Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms. Behav Brain Res 147:135–147

    Article  PubMed  CAS  Google Scholar 

  • Peterson JD, Wolf ME, White FJ (2003) Impaired DRL 30 performance during amphetamine withdrawal. Behav Brain Res 143:101–108

    Article  PubMed  CAS  Google Scholar 

  • Richards JB, Sabol KE, de Wit H (1999) Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology (Berl) 146:432–439

    Article  CAS  Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95(Suppl 2):S91–S117

    Article  PubMed  Google Scholar 

  • Robinson TE, Kolb B (1997) Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J Neurosci 17:8491–8497

    PubMed  CAS  Google Scholar 

  • Robinson TE, Kolb B (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur J Neurosci 11:1598–1604

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Becker JB, Moore CJ, Castaneda E, Mittleman G (1985) Enduring enhancement in frontal cortex dopamine utilization in an animal model of amphetamine psychosis. Brain Res 343:374–377

    Article  PubMed  CAS  Google Scholar 

  • Roesch MR, Takahashi Y, Gugsa N, Bissonette GB, Schoenbaum G (2007) Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude. J Neurosci 27:245–250

    Article  PubMed  CAS  Google Scholar 

  • Rogers RD, Everitt BJ, Baldacchino A, Blackshaw AJ, Swainson R, Wynne K, Baker NB, Hunter J, Carthy T, Booker E, London M, Deakin JF, Sahakian BJ, Robbins TW (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20:322–339

    Article  PubMed  CAS  Google Scholar 

  • Rosselli M, Ardila A (1996) Cognitive effects of cocaine and polydrug abuse. J Clin Exp Neuropsychol 18:122–135

    Article  PubMed  CAS  Google Scholar 

  • Segal DS, Mandell AJ (1974) Long-term administration of d-amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav 2:249–255

    Article  PubMed  CAS  Google Scholar 

  • Seiden LS, Sabol KE, Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol 33:639–677

    Article  PubMed  CAS  Google Scholar 

  • Simon NW, Mendez IA, Setlow B (2007) Cocaine exposure causes long-term increases in impulsive choice. Behav Neurosci 121:543–549

    Article  PubMed  CAS  Google Scholar 

  • Tenn CC, Fletcher PJ, Kapur S (2003) Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia. Schizophr Res 64:103–114

    Article  PubMed  Google Scholar 

  • Tenn CC, Kapur S, Fletcher PJ (2005) Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition. Psychopharmacology (Berl) 180:366–376

    Article  CAS  Google Scholar 

  • Uslaner JM, Robinson TE (2006) Subthalamic nucleus lesions increase impulsive action and decrease impulsive choice—mediation by enhanced incentive motivation? Eur J Neurosci 24:2345–2354

    Article  PubMed  Google Scholar 

  • van Gaalen MM, van Koten R, Schoffelmeer AN, Vanderschuren LJ (2006) Critical involvement of dopaminergic neurotransmission in impulsive decision making. Biol Psychiatry 60:66–73

    Article  PubMed  Google Scholar 

  • Verdejo-Garcia AJ, Perales JC, Perez-Garcia M (2007) Cognitive impulsivity in cocaine and heroin polysubstance abusers. Addict Behav 32:950–966

    Article  PubMed  Google Scholar 

  • Winstanley CA, Dalley JW, Theobald DE, Robbins TW (2003) Global 5-HT depletion attenuates the ability of amphetamine to decrease impulsive choice on a delay-discounting task in rats. Psychopharmacology (Berl) 170:320–331

    Article  CAS  Google Scholar 

  • Winstanley CA, LaPlant Q, Theobald DE, Green TA, Bachtell RK, Perrotti LI, DiLeone RJ, Russo SJ, Garth WJ, Self DW, Nestler EJ (2007) DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction. J Neurosci 27:10497–10507

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Alex Krueger, Acidalia Ortiz Rivera, and Sergei Pourmal for their technical assistance. This work was supported in part by a grant from the NIH (DA 019876), an Arnold O. Beckman Award from the University of Illinois, Urbana-Champaign, and a predoctoral fellowship to JJS (T32 NIH/HD007333).

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Authors and Affiliations

  1. Department of Psychology and Neuroscience Program, University of Illinois at Urbana-Champaign, 731 Psychology Bldg MC-716, 603 E Daniel St, Champaign, IL, 61820, USA

    Jessica J. Stanis, Hector Marquez Avila, Martin D. White & Joshua M. Gulley

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  1. Jessica J. Stanis
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  2. Hector Marquez Avila
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  3. Martin D. White
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  4. Joshua M. Gulley
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Correspondence to Joshua M. Gulley.

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Stanis, J.J., Marquez Avila, H., White, M.D. et al. Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task. Psychopharmacology 199, 539–548 (2008). https://doi.org/10.1007/s00213-008-1182-z

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  • DOI: https://doi.org/10.1007/s00213-008-1182-z

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