Skip to main content

Escalation of Drug Use

  • Protocol
  • First Online:
Animal Models of Drug Addiction

Part of the book series: Neuromethods ((NM,volume 53))

Abstract

Among the different behavioral criteria used to discriminate substance dependence (or drug addiction) from other non-disordered forms of drug use, drug intake escalation presents a number of unique features that makes it particularly suitable for modeling in nonhuman animals. This criterion has stood the passage of time despite major revisions of diagnostic systems, it is common to all known drugs of abuse and it can be readily and unambiguously operationalized in laboratory animals. Here I exhaustively review evidence showing that escalation to heavy consumption of different drugs (except perhaps nicotine) can be rapidly induced in the majority of individual animals (i.e., rats) by increased drug availability. Such an escalation of drug use is probably paralleled by an authentic escalation to drug addiction, as it is associated with the co-occurrence of other addiction-like changes (i.e., increased motivation for drug use; increased difficulty to abstain from drug use; decreased sensitivity to negative consequences). In addition, during escalation of drug intake, most individual animals become increasingly responsive to drug- and stress-primed, but apparently not cue-primed, reinstatement of drug seeking after extinction. Finally, following increased drug use, most individuals present selective cognitive dysfunctions (e.g., deficits in executive functions) that may contribute to the establishment and/or persistence of addiction. Thus, the study of individuals with escalating patterns of drug use should provide a unique and valid approach to investigate, experimentally, the behavioral and neurobiological mechanisms that underlie the progression to addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Edwards G, Gross MM (1976) Alcohol dependence: provisional description of a clinical syndrome. Br Med J 1:1058–1061

    PubMed  CAS  Google Scholar 

  2. Jaffe JH (1992) Current concepts of addiction. In: O’Brien CP, Jaffe JH (eds) Addictive states, Association for Research in Nervous and Mental Disease research publications, vol 70. Raven Press, New York, pp 1–21

    Google Scholar 

  3. Saunders JB (2006) Substance dependence and non-dependence in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD): can an identical conceptualization be achieved? Addiction 101(Suppl 1): 48–58

    PubMed  Google Scholar 

  4. Martin CS, Chung T, Langenbucher JW (2008) How should we revise diagnostic criteria for substance use disorders in the DSM-V? J Abnorm Psychol 117:561–575

    PubMed  Google Scholar 

  5. Wolffgramm J (1991) An ethopharmacological approach to the development of drug addiction. Neurosci Biobehav Rev 15:515–519

    PubMed  CAS  Google Scholar 

  6. Wolffgramm J, Heyne A (1995) From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat. Behav Brain Res 70:77–94

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  8. Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017

    PubMed  CAS  Google Scholar 

  9. Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ (2008) High impulsivity predicts the switch to compulsive cocaine-taking. Science 320:1352–1355

    PubMed  CAS  Google Scholar 

  10. Vanderschuren LJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019

    PubMed  CAS  Google Scholar 

  11. Negus SS (2006) Choice between heroin and food in nondependent and heroin-dependent rhesusmonkeys: effects of naloxone, buprenorphine, and methadone. J Pharmacol Exp Ther 317:711–723

    PubMed  CAS  Google Scholar 

  12. Panlilio LV, Goldberg SR (2007) Self-administration of drugs in animals and humans as a model and an investigative tool. Addiction 102:1863–1870

    PubMed  Google Scholar 

  13. Becker G, Murphy KM (1988) A theory of rational addiction. J Polit Econ 96:675–700

    Google Scholar 

  14. Shiffman S (1989) Tobacco “chippers” – individual differences in tobacco dependence. Psychopharmacology 97:539–547

    PubMed  CAS  Google Scholar 

  15. Hughes JR (2006) Should criteria for drug dependence differ across drugs? Addiction 101(Suppl 1):134–141

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Khantzian EJ (2003) Understanding addictive vulnerability: an evolving psychodynamic perspective. Neuropsychoanalysis 5:5–21

    Google Scholar 

  18. Redish AD, Jensen S, Johnson A (2008) A unified framework for addiction: vulnerabilities in the decision process. Behav Brain Sci 31:415–437

    PubMed  Google Scholar 

  19. Hursh SR (1991) Behavioral economics of drug self-administration and drug abuse policy. J Exp Anal Behav 56:377–393

    PubMed  CAS  Google Scholar 

  20. Westermeyer J (1999) The role of cultural and social factors in the cause of addictive disorders. Psychiatr Clin North Am 22:253–273

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  22. Dalley JW, Lääne K, Pena Y, Theobald DE, Everitt BJ, Robbins TW (2005) Attentional and motivational deficits in rats withdrawn from intravenous self-administration of cocaine or heroin. Psychopharmacology 182:579–587

    PubMed  CAS  Google Scholar 

  23. Dalley JW, Theobald DE, Berry D, Milstein JA, Lääne 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

    PubMed  CAS  Google Scholar 

  24. Dalley JW, Lääne K, Theobald DE et al (2007) Enduring deficits in sustained visual attention during withdrawal of intravenous methylenedioxymethamphetamine self-administration in rats: results from a comparative study with d-amphetamine and methamphetamine. Neuropsychopharmacology 32:1195–1206

    PubMed  CAS  Google Scholar 

  25. Dworkin SI, Goeders NE, Grabowski J, Smith JE (1987) The effects of 12-hour limited access to cocaine: reduction in drug intake and mortality. NIDA Res Monogr 76:221–225

    PubMed  CAS  Google Scholar 

  26. Piazza PV, Deminière JM, Le Moal M, Simon H (1989) Factors that predict individual vulnerability to amphetamine self-administration. Science 245:1511–1513

    PubMed  CAS  Google Scholar 

  27. Ahmed SH, Koob GF (2004) Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake. Psychopharmacology 172:450–454

    PubMed  CAS  Google Scholar 

  28. 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 86:102–113

    PubMed  CAS  Google Scholar 

  29. Ahmed SH, Kenny PJ, Koob GF, Markou A (2002) Neurobiological evidence for hedonic allostasis associated with escalating cocaine use. Nat Neurosci 5:625–626

    PubMed  CAS  Google Scholar 

  30. Ahmed SH, Lutjens R, van der Stap LD et al (2005) Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction. Proc Natl Acad Sci USA 102:11533–11538

    PubMed  CAS  Google Scholar 

  31. Ahmed SH, Cador M (2006) Dissociation of psychomotor sensitization from compulsive cocaine consumption. Neuropsycho-pharmacology 31:563–571

    PubMed  CAS  Google Scholar 

  32. Allen RM, Dykstra LA, Carelli RM (2007) Continuous exposure to the competitive N-methyl-D: -aspartate receptor antagonist, LY235959, facilitates escalation of cocaine consumption in Sprague-Dawley rats. Psychopharmacology 191:341–351

    PubMed  CAS  Google Scholar 

  33. Allen RM, Uban KA, Atwood EM, Albeck DS, Yamamoto DJ (2007) Continuous intracerebroventricular infusion of the competitive NMDA receptor antagonist, LY235959, facilitates escalation of cocaine self-administration andincreases break point for cocaine in Sprague-Dawley rats. Pharmacol Biochem Behav 88:82–88

    PubMed  CAS  Google Scholar 

  34. Aujla H, Martin-Fardon R, Weiss F (2008) Rats with extended access to cocaine exhibit increased stress reactivity and sensitivity to the anxiolytic-like effects of the mGluR 2/3 agonist LY379268 during abstinence. Neuropsychopharmacology 33:1818–1826

    PubMed  CAS  Google Scholar 

  35. Ben-Shahar O, Ahmed SH, Koob GF, Ettenberg A (2004) The transition from controlled to compulsive drug use is associated with a loss of sensitization. Brain Res 995:46–54

    PubMed  CAS  Google Scholar 

  36. Ben-Shahar O, Moscarello JM, Jacob B, Roarty MP, Ettenberg A (2005) Prolonged daily exposure to i.v. cocaine results in tolerance to its stimulant effects. Pharmacol Biochem Behav 82:411–416

    PubMed  CAS  Google Scholar 

  37. Ben-Shahar O, Moscarello JM, Ettenberg A (2006) One hour, but not six hours, of daily access to self-administered cocaine results in elevated levels of the dopamine transporter. Brain Res 1095:148–153

    PubMed  CAS  Google Scholar 

  38. Ben-Shahar O, Keeley P, Cook M et al (2007) Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine. Brain Res 1131:220–228

    PubMed  CAS  Google Scholar 

  39. Ben-Shahar O, Posthumus EJ, Waldroup SA, Ettenberg A (2008) Heightened drug-­seeking motivation following extended daily access to self-administered cocaine. Prog Neuropsychopharmacol Biol Psychiatry 32:863–869

    PubMed  CAS  Google Scholar 

  40. Briand LA, Gross JP, Robinson TE (2008) Impaired object recognition following prolonged withdrawal from extended-access cocaine self-administration. Neuroscience 155:1–6

    PubMed  CAS  Google Scholar 

  41. Briand LA, Flagel SB, Garcia-Fuster MJ et al (2008) Persistent alterations in cognitive function and prefrontal dopamine D2 receptors following extended, but not limited, access to self-administered cocaine. Neuropsychopharmacology 33:2969–2980

    PubMed  CAS  Google Scholar 

  42. 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 58:751–759

    PubMed  CAS  Google Scholar 

  43. Ferrario CR, Robinson TE (2007) Amphetamine pretreatment accelerates the subsequent escalation of cocaine self-adminis­tration behavior. Eur Neuropsycho-pharmacol 17:352–357

    PubMed  CAS  Google Scholar 

  44. Hansen ST, Mark GP (2007) The nicotinic acetylcholine receptor antagonist mecamylamine prevents escalation of cocaine self-administration in rats with extended daily access. Psychopharmacology 194:53–61

    PubMed  CAS  Google Scholar 

  45. Kenny PJ, Boutrel B, Gasparini F, Koob GF, Markou A (2005) Metabotropic glutamate 5 receptor blockade may attenuate cocaine self-administration by decreasing brain reward function in rats. Psychopharmacology 179:247–254

    PubMed  CAS  Google Scholar 

  46. Kippin TE, Fuchs RA, See RE (2006) Contributions of prolonged contingent and noncontingent cocaine exposure to enhanced reinstatement of cocaine seeking in rats. Psychopharmacology 187:60–67

    PubMed  CAS  Google Scholar 

  47. Knackstedt LA, Kalivas PW (2007) Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization. J Pharmacol Exp Ther 322:1103–1109

    PubMed  CAS  Google Scholar 

  48. Madayag A, Lobner D, Kau KS et al (2007) Repeated N-acetylcysteine administration alters plasticity-dependent effects of cocaine. J Neurosci 27:13968–13976

    PubMed  CAS  Google Scholar 

  49. Mantsch JR, Baker DA, Francis DM, Katz ES, Hoks MA, Serge JP (2008) Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats. Psychopharmacology 195:591–603

    PubMed  CAS  Google Scholar 

  50. Mantsch JR, Baker DA, Serge JP, Hoks MA, Francis DM, Katz ES (2008) Surgical adrenalectomy with diurnal corticosterone replacement slows escalation and prevents the augmentation of cocaine-induced reinstatement in ratsself-administering cocaine under long-access conditions. Neuropsychophar­macology 33:814–826

    PubMed  CAS  Google Scholar 

  51. Mantsch JR, Cullinan WE, Tang LC, Baker DA, Katz ES, Hoks MA, Ziegler DR (2007) Daily cocaine self-administration under long-access conditions augments restraint-induced increases in plasma corticosterone and impairs glucocorticoid receptor-mediated negative feedback in rats. Brain Res 1167:101–111

    PubMed  CAS  Google Scholar 

  52. 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. Neuropsycho-pharmacology 34:796–804

    PubMed  Google Scholar 

  53. Paterson NE, Markou A (2004) Prolonged nicotine dependence associated with ext­ended access to nicotine self-administration in rats. Psychopharmacology 173:64–72

    PubMed  CAS  Google Scholar 

  54. Perry JL, Morgan AD, Anker JJ, Dess NK, Carroll ME (2006) Escalation of i.v. cocaine self-administration and reinstatement of cocaine-seeking behavior in rats bred for high and low saccharin intake. Psychop­harmacology 186:235–245

    PubMed  CAS  Google Scholar 

  55. Roth ME, Carroll ME (2004) Sex differences in the escalation of intravenous cocaine intake following long-or short-access to cocaine self-administration. Pharmacol Biochem Behav 78:199–207

    PubMed  CAS  Google Scholar 

  56. Specio SE, Wee S, O’Dell LE, Boutrel B, Zorrilla EP, Koob GF (2008) CRF(1) receptor antagonists attenuate escalated cocaine self-administration in rats. Psychophar­macology 196:473–482

    PubMed  CAS  Google Scholar 

  57. Wee S, Mandyam CD, Lekic DM, Koob GF (2008) Alpha 1-noradrenergic system role in increased motivation for cocaine intake in rats with prolonged access. Eur Neuro­psychopharmacol 18:303–311

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  59. Larson EB, Anker JJ, Gliddon LA, Fons KS, Carroll ME (2007) Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access. Exp Clin Psychopharmacol 15:461–471

    PubMed  CAS  Google Scholar 

  60. Liu Y, Roberts DC, Morgan D (2005) Effects of extended-access self-administration and deprivation on breakpoints maintained by cocaine in rats. Psychopharmacology 179:644–651

    PubMed  CAS  Google Scholar 

  61. Mantsch JR, Yuferov V, Mathieu-Kia AM, Ho A, Kreek MJ (2004) Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats. Psychopharmacology 175:26–36

    PubMed  CAS  Google Scholar 

  62. Mandyam CD, Wee S, Eisch AJ, Richardson HN, Koob GF (2007) Methamphetamine self-administration and voluntary exercise have opposing effects on medial prefrontal cortex gliogenesis. J Neurosci 27:11442–11450

    PubMed  CAS  Google Scholar 

  63. Rogers JL, De Santis S, See RE (2008) Extended methamphetamine self-­administration enhances reinstatement of drug seeking and impairs novel object recognition in rats. Psychopharmacology 199:615–624

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  65. Kenny PJ, Markou A (2006) Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity. Neuropsychopharmacology 31:1203–1211

    PubMed  CAS  Google Scholar 

  66. Kenny PJ, Chen SA, Kitamura O, Markou A, Koob GF (2006) Conditioned withdrawal drives heroin consumption and decreases reward sensitivity. J Neurosci 26:5894–5900

    PubMed  CAS  Google Scholar 

  67. Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (2008) GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse. Proc Natl Acad Sci USA 105:8114–8119

    PubMed  CAS  Google Scholar 

  68. Wise RA (1973) Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacologia 29:203–210

    PubMed  CAS  Google Scholar 

  69. Simms JA, Steensland P, Medina B et al (2008) Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats. Alcohol Clin Exp Res 32:1816–1823

    PubMed  CAS  Google Scholar 

  70. O’Dell LE, Koob GF (2007) ‘Nicotine deprivation effect’ in rats with intermittent 23-hour access to intravenous nicotine self-administration. Pharmacol Biochem Behav 86:346–353

    PubMed  Google Scholar 

  71. George O, Ghozland S, Azar MR et al (2007) CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc Natl Acad Sci U S A 104:17198–17203

    PubMed  CAS  Google Scholar 

  72. Bozarth MA, Wise RA (1985) Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat. JAMA 254:81–83

    PubMed  CAS  Google Scholar 

  73. Morgan AD, Campbell UC, Fons RD, Carroll ME (2002) Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav 72:873–880

    PubMed  CAS  Google Scholar 

  74. Chen SA, O’Dell LE, Hoefer ME, Greenwell TN, Zorrilla EP, Koob GF (2006) Unlimited access to heroin self-administration: independent motivational markers of opiate dependence. Neuropsychopharmacology 31:2692–2707 [Erratum, Neuropsycho-pharmacology 2006;31:2802]

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  76. Lenoir M, Cantin L, Serre F, Ahmed SH (2008) The value of heroin increases with extended use but not above the value of a non-essential alternative reward. In: 38th annual meeting of the society for neuroscience, Washington, DC, 14–19 November 2008

    Google Scholar 

  77. Lenoir M, Ahmed SH (2007) Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization. Neuropsychophar­macology 32:616–624

    PubMed  CAS  Google Scholar 

  78. Lenoir M, Ahmed SH (2008) Supply of a nondrug substitute reduces escalated heroin consumption. Neuropsychopharmacology 33:2272–2282

    PubMed  Google Scholar 

  79. Doherty J, Ogbomnwan Y, Williams B, Frantz K (2009) Age-dependent morphine intake and cue-induced reinstatement, but not escalation in intake, by adolescent and adult male rats. Pharmacol Biochem Behav 92:164–172

    PubMed  CAS  Google Scholar 

  80. Mormede P, Colas A, Jones BC (2004) High ethanol preferring rats fail to show dependence following short- or long-term ethanol exposure. Alcohol Alcohol 39:183–189

    PubMed  CAS  Google Scholar 

  81. Ward SJ, Läck C, Morgan D, Roberts DC (2006) Discrete-trials heroin self-administration produces sensitization to the reinforcing effects of cocaine in rats. Psychopharmacology 185:150–159

    PubMed  CAS  Google Scholar 

  82. Winger G, Woods JH (2001) The effects of chronic morphine on behavior reinforced by several opioids or by cocaine in rhesus monkeys. Drug Alcohol Depend 62:181–189

    PubMed  CAS  Google Scholar 

  83. Ahmed SH, Bobashev G, Gutkin BS (2007) The simulation of addiction: pharmacological and neurocomputational models of drug self-administration. Drug Alcohol Depend 90:304–311

    PubMed  CAS  Google Scholar 

  84. Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology 189:1–16

    PubMed  CAS  Google Scholar 

  85. Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989) Cocaine-induced cocaine craving. Psychopharmacology 97:59–64

    PubMed  CAS  Google Scholar 

  86. Volkow ND, Wang GJ, Ma Y et al (2005) Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: relevance to addiction. J Neurosci 25:3932–3939

    PubMed  CAS  Google Scholar 

  87. Bickel WK, DeGrandpre RJ, Higgins ST, Hughes JR (1990) Behavioral economics of drug self-administration. I. Functional equivalence of response requirement and drug dose. Life Sci 47:1501–1510

    PubMed  CAS  Google Scholar 

  88. Zittel-Lazarini A, Cador M, Ahmed SH (2007) A critical transition in cocaine self-administration: behavioral and neurobiological implications. Psychopharmacology 192:337–346

    PubMed  CAS  Google Scholar 

  89. Christensen CJ, Silberberg A, Hursh SR, Roma PG, Riley AL (2008) Demand for cocaine and food over time. Pharmacol Biochem Behav 91:209–216

    PubMed  CAS  Google Scholar 

  90. Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134:943–944

    PubMed  CAS  Google Scholar 

  91. Arnold JM, Roberts DC (1997) A critique of fixed and progressive ratio schedules used to examine the neural substrates of drug reinforcement. Pharmacol Biochem Behav 57:441–447

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  93. Wee S, Wang Z, Woolverton WL, Pulvirenti L, Koob GF (2007) Effect of aripiprazole, a partial dopamine D2 receptor agonist, on increased rate of methamphetamine self-administration in rats with prolonged session duration. Neuropsychopharmacology 32:2238–2247

    PubMed  CAS  Google Scholar 

  94. Li DH, Depoortere RY, Emmett-Oglesby MW (1994) Tolerance to the reinforcing effects of cocaine in a progressive ratio paradigm. Psychopharmacology 116:326–332

    PubMed  CAS  Google Scholar 

  95. Zhou W, Zhang F, Liu H, Tang S, Lai M, Zhu H, Kalivas PW (2009) Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse. Psychopharmacology 203:677–684

    PubMed  CAS  Google Scholar 

  96. Sorge RE, Stewart J (2005) The contribution of drug history and time since termination of drug taking to footshock stress-induced cocaine seeking in rats. Psychopharmacology 183:210–217

    PubMed  CAS  Google Scholar 

  97. Grimm JW, Hope BT, Wise RA, Shaham Y (2001) Neuroadaptation: incubation of cocaine craving after withdrawal. Nature 412:141–142

    PubMed  CAS  Google Scholar 

  98. Campbell ND (2007) Discovering addiction: the science and politics of substance abuse research. The University of Michigan Press, Ann Arbor

    Google Scholar 

  99. Deneau G, Yanagita T, Seevers MH (1969) Self-administration of psychoactive substances by the monkey. Psychopharmacologia 16:30–48

    PubMed  CAS  Google Scholar 

  100. Sutton MA, Karanian DA, Self DW (2000) Factors that determine a propensity for cocaine-seeking behavior during abstinence in rats. Neuropsychopharmacology 22:626–641

    PubMed  CAS  Google Scholar 

  101. Baker DA, Tran-Nguyen TL, Fuchs RA, Neisewander JL (2001) Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats. Psychopharmacology 155:18–26

    PubMed  CAS  Google Scholar 

  102. Mantsch JR, Ho A, Schlussman SD, Kreek MJ (2001) Predictable individual differences in the initiation of cocaine self-administration by rats under extended-access conditions are dose-dependent. Psychopharmacology 157:31–39

    PubMed  CAS  Google Scholar 

  103. Edwards S, Whisler KN, Fuller DC, Orsulak PJ, Self DW (2007) Addiction-related alterations in D1 and D2 dopamine receptor behavioral responses following chronic cocaine self-administration. Neuropsycho­pharmacology 32:354–366

    PubMed  CAS  Google Scholar 

  104. Dalley JW, Fryer TD, Brichard L et al (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315:1267–1270

    PubMed  CAS  Google Scholar 

  105. Heyne A, Wolffgramm J (1998) The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate. Psychopharmacology 140:510–518

    PubMed  CAS  Google Scholar 

  106. Anker JJ, Perry JL, Gliddon LA, Carroll ME. (2009) Impulsivity predicts the escalation of cocaine self-administration in rats. Pharmacol Biochem Behav 93:343–8.

    PubMed  CAS  Google Scholar 

  107. Quadros IM, Miczek KA (2009) Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats. Psychopharmacology 206:109–20.)

    Google Scholar 

  108. Ahmed SH (2005) Imbalance between drug and non-drug reward availability: a major risk factor for addiction. Eur J Pharmacol 526:9–20

    PubMed  CAS  Google Scholar 

  109. Winstanley CA, Bachtell RK, Theobald DE et al (2009) Increased impulsivity during withdrawal from cocaine self-administration: role for DeltaFosB in the orbitofrontal cortex. Cereb Cortex 19:435–444

    PubMed  Google Scholar 

  110. Perry JL, Nelson SE, Carroll ME (2008) Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats. Exp Clin Psychopharmacol 16:165–177

    PubMed  Google Scholar 

  111. Calu DJ, Stalnaker TA, Franz TM, Singh T, Shaham Y, Schoenbaum G (2007) Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats. Learn Mem 14:325–328

    PubMed  Google Scholar 

  112. Liu S, Heitz RP, Sampson AR, Zhang W, Bradberry CW (2008) Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration. Cereb Cortex 18:2109–2116

    PubMed  CAS  Google Scholar 

  113. Diergaarde L, Pattij T, Poortvliet I, Hogenboom F, de Vries W, Schoffelmeer AN, De Vries TJ (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiatry 63:301–308

    PubMed  CAS  Google Scholar 

  114. Shaffer HJ, Eber GB (2002) Temporal progression of cocaine dependence symptoms in the US National Comorbidity Survey. Addiction 97:543–554

    PubMed  Google Scholar 

  115. Lenoir M, Serre F, Cantin L, Ahmed SH (2007) Intense sweetness surpasses cocaine reward. PLoS ONE 2:e698

    PubMed  Google Scholar 

  116. Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11–34

    PubMed  CAS  Google Scholar 

  117. Mantsch JR, Katz ES (2007) Elevation of glucocorticoids is necessary but not sufficient for the escalation of cocaine self-administration by chronic electric footshock stress in rats. Neuropsychopharmacology 32:367–376

    PubMed  CAS  Google Scholar 

  118. Czoty PW, Reboussin BA, Calhoun TL, Nader SH, Nader MA (2007) Long-term cocaine self-administration under fixed-ratio and second-order schedules in monkeys. Psychopharmacology 191:287–295

    PubMed  CAS  Google Scholar 

  119. Henry PK, Howell LL (2009) Cocaine-induced reinstatement during limited and extended drug access conditions in rhesus monkeys. Psychopharmacology 204:523–529

    PubMed  CAS  Google Scholar 

  120. Lattanzio SB, Eikelboom R (2003) Wheel access duration in rats: I. Effects on feeding and running. Behav Neurosci 117:496–504

    PubMed  Google Scholar 

  121. 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 93:67–74

    PubMed  CAS  Google Scholar 

  122. George O, Mandyam CD, Wee S, Koob GF (2008) Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments. Neuropsychopharmacology 33:2474–2482

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the French Research Council (CNRS), Université Victor-Segalen Bordeaux 2 and Mission Interministérielle de Lutte contre la Drogue et la Toxicomaine (MILDT). I thank Drs. Magalie Lenoir, Karyn Guillem, and Kelly Clemens for their comments on a previous draft of this book chapter. I also thank the reviewer and the editor for their constructive comments. I dedicate this book chapter to my wife, Dr. Saloua Aidoudi.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Ahmed, S.H. (2011). Escalation of Drug Use. In: Olmstead, M. (eds) Animal Models of Drug Addiction. Neuromethods, vol 53. Humana Press. https://doi.org/10.1007/978-1-60761-934-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-934-5_10

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-933-8

  • Online ISBN: 978-1-60761-934-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics