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Escalation of cocaine intake with extended access in rats: dysregulated addiction or regulated acquisition?

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Abstract

Rationale

Understanding the neurobehavioral mechanisms underlying dysregulated cocaine intake is important for the development of new cocaine abuse therapies.

Objectives

The current study determined if cocaine escalation under extended access conditions (6-h access) is regulated by discrimination learning processes.

Methods

Rats were initially trained on cocaine self-administration (0.1 or 0.25 mg/kg/infusion) using a fixed ratio 1 (FR 1) schedule under 1-h access for 12 sessions. Some rats were then trained to self-administer cocaine under 1-h or 6-h access conditions exclusively for 14 additional sessions, while other rats were trained under both 1- and 6-h access conditions that were cued or noncued for 28 additional sessions (14 sessions for each 1- and 6-h access). Two additional groups of rats were initially trained to self-administer cocaine using an FR 1 schedule under 10-min access for 12 sessions; half of the animals were then switched to 60-min access conditions for 14 additional sessions.

Results

When access conditions were differentially cued, escalation of cocaine intake was evident in animals with both 1- and 6-h access conditions during the escalation phase. Escalation also was evident in animals initially trained with 10-min access and then switched to 60-min access.

Conclusions

The results demonstrate that dysregulated and regulated intakes can be expressed within the same animal, indicating that escalation is context-dependent. Furthermore, escalated cocaine intake can be expressed under 1-h access conditions. Overall, these results suggest that escalated cocaine intake may be representative of discrimination-dependent regulated intake rather than addiction-like, compulsive intake.

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References

  • Ahmed SH (2009) Escalation of drug use. In: Olmstead MC (ed) Neuromethods: animal models of drug addiction. The Humana Press Inc., New Jersey

    Google Scholar 

  • Ahmed SH, Cador M (2006) Dissociation of psychomotor sensitization from compulsive cocaine consumption. Neuropsychopharmacology 31(3):563–571

    Article  PubMed  CAS  Google Scholar 

  • Ahmed SH, Koob GF (1998) Transition from moderate to excessive drug intake: change in hedonic set point. Science 282(5387):298–300

    Article  PubMed  CAS  Google Scholar 

  • Ahmed SH, Koob GF (1999) Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology (Berl) 146(3):303–312

    Article  CAS  Google Scholar 

  • Ahmed SH, Koob GF (2004) Changes in response to dopamine receptor antagonists in rats with escalating cocaine intake. Psychopharmacology (Berl) 172(4):450–454

    Article  CAS  Google Scholar 

  • Ahmed SH, Koob GF (2005) Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function. Psychopharmacology (Berl) 180(3):473–490

    Article  CAS  Google Scholar 

  • Ahmed H, Walker JR, Koob GF (2000) Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22(4):413–421

    Article  PubMed  CAS  Google Scholar 

  • Ahmed SH, Lin D, Koob GF, Parsons LH (2003) Escalation of cocaine self-administration does not depend on altered cocaine-induced nucleus accumbens dopamine levels. J Neurochem 86(1):102–113

    Article  PubMed  CAS  Google Scholar 

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Publishing, Washington, DC

    Google Scholar 

  • Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology (Berl) 191(3):391–431

    Article  CAS  Google Scholar 

  • Carroll ME, Batulis DK, Landry KL, Morgan AD (2005) Sex differences in the escalation of oral phencyclidine (PCP) self-administration under FR and PR schedules in rhesus monkeys 180(3):414–426

  • Edwards S, Bachtell RK, Guzman D, Whistler KN, Self DW (2011) Emergence of context-associated GluR(1) and ERK phosphorylation in the nucleus accumbens core during withdrawal from cocaine self-administration. Addict Biol 16(3):450–457

    Article  PubMed  CAS  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8(11):1481–1489

    Article  PubMed  CAS  Google Scholar 

  • Ferrario CR, Gorny G, Crombag HS, Li Y, Kolb B, Robinson TE (2005) Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use. Biol Psychiatry 58(9):751–759

    Article  PubMed  CAS  Google Scholar 

  • Fitch TE, Roberts DC (1993) The effects of dose and access restrictions on periodicity of cocaine self-administration in the rat. Drug Alcohol Depend 33(2):119–128

    Article  PubMed  CAS  Google Scholar 

  • Gibbon J, Church RM, Meck WH (1984) Scalar timing in memory. Ann N Y Acad Sci 423:52–77

    Article  PubMed  CAS  Google Scholar 

  • Gipson CD, Bardo MT (2009) Extended access to d-amphetamine self-administration increases impulsive choice in a delay discounting task in rats. Psychopharmacology (Berl) 207(3):391–400

    Article  CAS  Google Scholar 

  • Gipson CD, Beckmann JS, El-Maraghi S, Marusich JA, Bardo MT (2011) Effect of environmental enrichment on escalation of cocaine self-administration in rats. Psychopharmacology (Berl) 214(2):557–566

    Article  CAS  Google Scholar 

  • Goeders JE, Murnane KS, Banks ML, Fantegrossi WE (2009) Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice. Pharmacol Biochem Behav 93(1):67–74

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, O’Brien C (2008) Drug addiction as a pathology of staged neuroplasticity. Neuropsychopharmacology 33(1):166–180

    Article  PubMed  CAS  Google Scholar 

  • Kitamura O, Wee S, Specio SE, Koob GF, Pulvirenti L (2006) Escalation of methamphetamine self-administration in rats: a dose effect function. Psychopharmacology (Berl) 186(1):48–53

    Article  CAS  Google Scholar 

  • Koob GF, Ahmed SH, Boutrel B, Chen SA, Kenny PJ et al (2004) Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev 27(8):739–749

    Article  PubMed  CAS  Google Scholar 

  • Madayag A, Kau KS, Lobner D, Mantsch JR, Wisniewski S, Baker DA (2010) Drug-induced plasticity contributing to heightened relapse susceptibility: neurochemical changes and augmented reinstatement in high-intake rats. J Neurosci 30(1):210–217

    Article  PubMed  CAS  Google Scholar 

  • Marusich JA, Beckmann JS, Gipson CD, Bardo MT (2010) Methylphenidate as a reinforcer for rats: contingent delivery and intake escalation. Exp Clin Psychopharmacol 18(3):257–266

    Article  PubMed  CAS  Google Scholar 

  • Oleson EB, Roberts DC (2009) Behavioral economic assessment of price and cocaine consumption following self-administration histories that produce escalation of either final ratios or intake. Neuropsychopharmacology 34(3):796–804

    Article  PubMed  Google Scholar 

  • Paterson NE, Markou A (2003) Increased motivation for self-administered cocaine after escalated cocaine intake. Neuroreport 14(17):2229–2232

    Article  PubMed  CAS  Google Scholar 

  • Roberts DC, Brebner K, Vincler M, Lynch WJ (2002) Patterns of cocaine self-administration in rats produced by various access conditions under a discrete trials procedure. Drug Alcohol Depend 67(3):291–299

    Article  PubMed  CAS  Google Scholar 

  • Roberts DC, Morgan D, Liu Y (2007) How to make a rat addicted to cocaine. Prog Neuropsychopharmacol Biol Psychiatry 31(8):1614–1624

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2008) Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond B Biol Sci 363(1507):3137-3146

    Google Scholar 

  • Siegel S (1976) Morphine analgesic tolerance: its situation specificity supports a Pavlovian conditioning model. Science 194(4250):323–325

    Article  Google Scholar 

  • Tornatzky W, Miczek KA (2000) Cocaine self-administration “binges”: transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats. Psychopharmacology (Berl) 148(3):289–298

    Article  CAS  Google Scholar 

  • Tsibulsky VL, Norman AB (1999) Satiety threshold: a quantitative model of maintained cocaine self-administration. Brain Res 839(1):85–93

    Article  PubMed  CAS  Google Scholar 

  • Wee S, Specio SE, Koob GF (2007) Effects of dose and session duration on cocaine self-administration in rats. J Pharmacol Exp Ther 320(3):1134–1143

    Article  PubMed  CAS  Google Scholar 

  • Zernig G, Ahmed SH, Cardinal RN, Morgan D, Acquas E, Foltin RW, Vezina P et al (2007) Explaining the escalation of drug use in substance dependence: models and appropriate animal laboratory tests. Pharmacology 80(2–3):65–119

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by National Institutes of Health, National Institute on Drug Abuse [P50 DA05312 and T32 DA01617]

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Authors and Affiliations

  1. Department of Psychology, University of Kentucky, 741 S. Limestone, 448C BBSRB, Lexington, KY, 40536-0509, USA

    Joshua S. Beckmann & Michael T. Bardo

  2. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA

    Cassandra D. Gipson

  3. Discovery and Analytical Sciences, RTI, International, Research Triangle Park, NC, USA

    Julie A. Marusich

Authors
  1. Joshua S. Beckmann
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  2. Cassandra D. Gipson
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  3. Julie A. Marusich
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  4. Michael T. Bardo
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Correspondence to Joshua S. Beckmann.

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Beckmann, J.S., Gipson, C.D., Marusich, J.A. et al. Escalation of cocaine intake with extended access in rats: dysregulated addiction or regulated acquisition?. Psychopharmacology 222, 257–267 (2012). https://doi.org/10.1007/s00213-012-2641-0

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  • DOI: https://doi.org/10.1007/s00213-012-2641-0

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