Skip to main content
Log in

Escalation of intravenous cocaine self-administration, progressive-ratio performance, and reinstatement in rats selectively bred for high (HiS) and low (LoS) saccharin intake

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

An Erratum to this article was published on 17 March 2005

Abstract

Rationale

Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (IV) cocaine self-administration more rapidly than their low saccharin (LoS) consuming counterparts.

Objectives

The purpose of the present study was to determine whether HiS and LoS rats also differ in the escalation, maintenance, and reinstatement of IV cocaine self-administration.

Methods

LoS and HiS female rats were allowed to self-administer cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long (LgA, 12 h per day) access conditions for 21 days. Session lengths were subsequently equated (2 h) and (1) FR1-maintained cocaine (0.4 mg/kg) self-administration, (2) progressive ratio (PR)-maintained cocaine (0.2–1.6 mg/kg) self-administration, and (3) saline-induced and cocaine (10 mg/kg, IP)-induced reinstatement of drug-seeking behavior were examined.

Results

HiS LgA rats escalated their cocaine intake more rapidly and self-administered more cocaine (mg/kg) than LoS LgA rats; however, there was no LoS versus HiS phenotype difference in the number of infusions self-administered by Day 21. Post-escalation cocaine self-administration under an FR1 schedule did not differ as a function of phenotype (LoS versus HiS) or access condition (ShA versus LgA); however, LoS rats responded more for cocaine under the PR schedule than HiS rats, and they showed a greater reinstatement of cocaine-seeking behavior than HiS rats. In contrast, ShA versus LgA did not affect PR or reinstatement performance in the LoS and HiS groups.

Conclusions

These results suggest that LoS and HiS rats have distinct drug-seeking and drug-taking profiles that differ as a function of the experimental phase and access condition. The LoS and HiS rats differ along a wide range of behavioral dimensions and represent an important model to study the interactions of feeding, emotionality, and other factors related to vulnerability to drug abuse.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Badia-Elder N, Kiefer SW, Dess NK (1996) Taste reactivity in rats selectively bred for high versus. low saccharin consumption. Physiol Behav 59:749–755

    Article  CAS  PubMed  Google Scholar 

  • Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510

    CAS  PubMed  Google Scholar 

  • Carroll ME (1993) The economic context of drug and non-drug reinforcers affects acquisition and maintenance of drug-reinforced behavior and withdrawal effects. Drug Alcohol Depend 33:201–210

    Article  CAS  PubMed  Google Scholar 

  • Carroll ME (1999) Interactions between food and addiction. In: Niesink RJM, Hoefakker RE, Westera W, Jaspers RMA, Kornet LMW, Boobis S (eds) Neurobehavioral toxicology and addiction: food, drugs and environment. CRC, Boca Raton, pp 286–311

    Google Scholar 

  • Carroll ME, Campbell UC (2000) A behavioral economic analysis of the reinforcing effects of drugs: transition states of addiction. In: Bickel WK, Vuchinich RE (eds) Reframing health behavior change with behavioral economics. Lawrence Erlbaum, Mahwah, pp 63–87

    Google Scholar 

  • Carroll ME, Comer SD (1996) Animal models of relapse. Exp Clin Psychopharmacol 4:11–18

    Article  CAS  Google Scholar 

  • Carroll ME, Morgan AD, Lynch WJ, Campbell UC, Dess NK (2002) Intravenous cocaine and heroin self-administration in rats selectively bred for differential saccharin intake: phenotype and sex differences. Psychopharmacology 161:304–313

    Article  CAS  PubMed  Google Scholar 

  • Carroll ME, Lynch WC, Roth ME, Morgan AD, Cosgrove KP (2004) Sex and estrogen influence drug abuse. Trends Pharmacol Sci (in press)

  • Cools AR, Gingras MA (1998) Nijmegen high and low responders to novelty: a new tool in the search after the neurobiology of drug abuse liability. Pharmacol Biochem Behav 60:151–159

    Google Scholar 

  • Crabbe JC (2002) Genetic contributions to addiction. Annu Rev Psychol 53:435–462

    Article  PubMed  Google Scholar 

  • Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H (1996) Novelty-seeking in rats—biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 34:136–145

    CAS  PubMed  Google Scholar 

  • Dess NK, Minor TR (1996) Taste and emotionality in rats selectively bred for high versus low saccharin intake. Anim Learn Behav 24:105–115

    Google Scholar 

  • Dess NK, Badia-Elder NE, Thiele TE, Kiefer SW, Blizard DA (1998) Ethanol consumption in rats selectively bred for differential saccharin intake. Alcohol 16:275–278

    Article  CAS  PubMed  Google Scholar 

  • Dess NK, Arnal J, Chapman CD, Siebel S, VanderWeele DA (2002) Exploring adaptations to famine: rats selectively bred for differential intake of saccharin differ on deprivation-induced hyperactivity and emotionality. Int J Comp Psychol 13:34–52

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gahtan E, Labounty LP, Wyvell C, Carroll ME (1996) The relationships among saccharin consumption, oral ethanol, and IV cocaine self-administration. Pharmacol Biochem Behav 53:919–925

    Google Scholar 

  • Goeders NE (2002) Stress and cocaine addiction. J Pharmacol Exp Ther 301:785–789

    Article  CAS  PubMed  Google Scholar 

  • Gosnell BA, Krahn DD (1992) The relationship between saccharin and alcohol intake in rats. Alcohol 9:203–206

    Article  CAS  PubMed  Google Scholar 

  • Gosnell BA, Krahn DD (1998) Taste and diet preferences as predictors of drug self-administration. NIDA Res Monogr 169:154–175

    CAS  PubMed  Google Scholar 

  • Haile CN, Kosten TA (2000) Differential effects of D1-and D2-like compounds on the discriminative stimulus and reinforcing effects of cocaine in Lewis and Fischer rats. College on problems of drug dependence. Drug and alcohol dependence. Elsevier, San Juan

    Google Scholar 

  • Haile CN, Kosten TA (2001) Differential effects of D1- and D2-like compounds on cocaine self-administration in Lewis and Fischer 344 inbred rats. J Pharmacol Exp Ther 299:509–518

    CAS  PubMed  Google Scholar 

  • Homberg JR, van den Akker M, Raaso HS, Wardeh G, Binnekade R, Schoffelmeer AN, de Vries TJ (2002) Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci 15:1542–1550

    Article  PubMed  Google Scholar 

  • Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB Jr (1991a) Individual differences in locomotor activity and sensitization. Pharmacol Biochem Behav 38:467–470

    Article  CAS  PubMed  Google Scholar 

  • Hooks MS, Jones GH, Smith AD, Neill DB, Justice JB Jr (1991b) Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine. Synapse 9:121–128

    CAS  PubMed  Google Scholar 

  • Johanson CE, Balster RL, Bonese K (1976) Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Pharmacol Biochem Behav 4:45–51

    Article  CAS  PubMed  Google Scholar 

  • Kampov-Polevoy AB, Overstreet DH, Rezvani AH, Janowsky DS (1995) Suppression of ethanol intake in alcohol-preferring rats by prior voluntary saccharin consumption. Pharmacol Biochem Behav 52:59–64

    Google Scholar 

  • Kampov-Polevoy AB, Garbutt JC, Janowsky DS (1999) Association between preference for sweets and excessive alcohol intake: a review of animal and human studies. Alcohol Alcohol 34:386–395

    Article  CAS  PubMed  Google Scholar 

  • Koros E, Piasecki J, Kostowski W, Bienkowski P (1998) Saccharin drinking rather than open field behaviour predicts initial ethanol acceptance in Wistar rats. Alcohol Alcohol 33:131–140

    CAS  PubMed  Google Scholar 

  • Kosten TA, Miserendino MJ, Haile CN, DeCaprio JL, Jatlow PI, Nestler EJ (1997) Acquisition and maintenance of intravenous cocaine self-administration in Lewis and Fischer inbred rat strains. Brain Res 778:418–429

    Article  CAS  PubMed  Google Scholar 

  • Levine AS, Kotz CM, Gosnell BA (2003a) Sugars and fats: the neurobiology of preference. J Nutr 133:831S–834S

    CAS  PubMed  Google Scholar 

  • Levine AS, Kotz CM, Gosnell BA (2003b) Sugars: hedonic aspects, neuroregulation, and energy balance. Am J Clin Nutr 78:834S–842S

    CAS  PubMed  Google Scholar 

  • Li TK, Lumeng L, Doolittle DP (1993) Selective breeding for alcohol preference and associated responses. Behav Genet 23:163–170

    CAS  PubMed  Google Scholar 

  • Lynch WJ, Roth ME, Carroll ME (2002) Biological basis of sex differences in drug abuse: preclinical and clinical studies. Psychopharmacology 164:121–137

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • McClearn GE, Rodgers DA (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:691–695

    Google Scholar 

  • 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

    Google Scholar 

  • National Research Council (2003) Guide for the care and use of mammals in neuroscience and behavioral research. The National Academies, Washington

    Google Scholar 

  • Nestler EJ (2000) Genes and addiction. Nat Genet 26:277–281

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Piazza PV, Deminiere JM, Maccari S, Mormede P, Le Moal M, Simon H (1990) Individual reactivity to novelty predicts probability of amphetamine self-administration. Behav Pharmacol 1:339–345

    PubMed  Google Scholar 

  • Piazza PV, Deroche V, Rouge-Pont F, Le Moal M (1998) Behavioral and biological factors associated with individual vulnerability to psychostimulant abuse. NIDA Res Monogr 169:105–133

    CAS  PubMed  Google Scholar 

  • Ramos A, Mormede P (1998) Stress and emotionality: a multidimensional and genetic approach. Neurosci Biobehav Rev 22:33–57

    Article  CAS  PubMed  Google Scholar 

  • Ranaldi R, Bauco P, McCormick S, Cools AR, Wise RA (2001) Equal sensitivity to cocaine reward in addiction-prone and addiction-resistant rat genotypes. Behav Pharmacol 12:527–534

    CAS  PubMed  Google Scholar 

  • Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Rowlett JK (2000) A labor-supply analysis of cocaine self-administration under progressive-ratio schedules: antecedents, methodologies, and perspectives. Psychopharmacology 153:1–16

    Article  CAS  PubMed  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20

    Article  CAS  PubMed  Google Scholar 

  • Sinclair JD, Kampov-Polevoy A, Stewart R, Li TK (1992) Taste preferences in rat lines selected for low and high alcohol consumption. Alcohol 9:155–160

    Article  CAS  PubMed  Google Scholar 

  • Stafford D, LeSage MG, Glowa JR (1998) Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review. Psychopharmacology 139:169–184

    Article  CAS  PubMed  Google Scholar 

  • VanderWeele DA, Dess NK, Castonguay TW (2002) Ingestional responses to metabolic challenges in rats selectively bred for high and low saccharin intake. Physiol Behav 75:97–104

    Article  CAS  PubMed  Google Scholar 

  • Vries TJ de, Schoffelmeer AN, Binnekade R, Mulder AH, Vanderschuren LJ (1998) Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization. Eur J Neurosci 10:3565–3571

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Jennifer L. Perry and Erin B. Larson for careful reading of this manuscript, and Annemarie K. Loth, Justin Anker, and Marissa M. Anderson for their technical assistance. This work was supported by NIH grants T32 DA07097 (A.D.M.), RO1 DA03240, and K05 DA15267 (M.E.C.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrew D. Morgan.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-005-2245-z

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morgan, A.D., Dess, N.K. & Carroll, M.E. Escalation of intravenous cocaine self-administration, progressive-ratio performance, and reinstatement in rats selectively bred for high (HiS) and low (LoS) saccharin intake. Psychopharmacology 178, 41–51 (2005). https://doi.org/10.1007/s00213-004-1979-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-004-1979-3

Keywords

Navigation