Skip to main content
SpringerLink
Log in

Abstinence-dependent transfer of lithium chloride-induced sucrose aversion to a sucrose-paired cue in rats

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

Abstract

Rationale

Responding for a drug- or sucrose-paired cue increases over forced abstinence (incubation of craving). If the incentive value of a cue depends on the incentive value of the primary reward, devaluing the primary reward should reduce cue reactivity.

Objectives

We investigated whether conditioned taste aversion (CTA) to sucrose would transfer to a sucrose-paired cue after 1 or 30 days of forced abstinence and whether CTA after 1 day of forced abstinence would affect incubation of craving.

Materials and methods

Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After 1 (Exp.1) or 30 (Exp.2) days of forced abstinence, rats received two home-cage pairings of sucrose with either LiCl (65 mg/kg, IP) to produce CTA or saline as a control. Two days later, rats responded for the cue alone. The following day, sucrose consumption was assessed in the same operant conditioning chamber. Exp.1 rats were tested again 1 month later to determine if CTA would affect incubation of craving.

Results

Exp.1: CTA after 1 day of forced abstinence did not attenuate cue reactivity when tested immediately after CTA, nor did the treatment affect incubation of craving or incubation of sucrose consumption. Exp.2: CTA after 1 month of forced abstinence resulted in a significant reduction in cue reactivity.

Conclusion

The incentive values of sucrose and the conditioned representation of sucrose increase over an extended period of forced abstinence. This incubation appears to facilitate the transfer of an aversion to the primary reward to the conditioned cue.

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

Access this article

Log in via an institution

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Balleine BW, Delgado MR, Hikosaka O (2007) The role of the dorsal striatum in reward and decision-making. J Neurosci 27:8161–8165

    Article  CAS  PubMed  Google Scholar 

  • Banys P (1988) The clinical use of disulfiram (Antabuse): a review. J Psychoactive Drugs 20:243–261

    CAS  PubMed  Google Scholar 

  • Bergquist KL, Paliwal P, Hyman SM, Sinha R (2006) Changes in cocaine craving, mood and stress in cocaine-dependent individuals during inpatient treatment and outpatient follow-up college on problems of drug dependence annual meeting, poster #67

  • Bermudez-Rattoni F, Grijalva CV, Kiefer SW, Garcia J (1986) Flavor-illness aversions: the role of the amygdala in the acquisition of taste-potentiated odor aversions. Physiol Behav 38:503–508

    Article  CAS  PubMed  Google Scholar 

  • Burns LH, Robbins TW, Everitt BJ (1993) Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of D-amphetamine. Behav Brain Res 55:167–183

    Article  CAS  PubMed  Google Scholar 

  • Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP (1999) Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156:11–18

    CAS  PubMed  Google Scholar 

  • Conrad KL, Tseng KY, Uejima JL, Reimers JM, Heng LJ, Shaham Y, Marinelli M, Wolf ME (2008) Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature 454:118–121

    Article  CAS  PubMed  Google Scholar 

  • Di Ciano P, Everitt BJ (2004) Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: implications for the persistence of addictive behaviour. Neuropharmacology 47(Suppl 1):202–213

    PubMed  Google Scholar 

  • Fenu S, Di Chiara G (2003) Facilitation of conditioned taste aversion learning by systemic amphetamine: role of nucleus accumbens shell dopamine D1 receptors. Eur J Neurosci 18:2025–2030

    Article  PubMed  Google Scholar 

  • Grimm JW, Kruzich PJ, See RE (2000) Contingent access to stimuli associated with cocaine self-administration is required for reinstatement of drug-seeking behavior. Psychobiology 28:383–386

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Grimm JW, Lu L, Hayashi T, Hope BT, Su TP, Shaham Y (2003) Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. J Neurosci 23:742–747

    CAS  PubMed  Google Scholar 

  • Grimm JW, Fyall AM, Osincup DP (2005) Incubation of sucrose craving: effects of reduced training and sucrose pre-loading. Physiol Behav 84:73–79

    Article  CAS  PubMed  Google Scholar 

  • Grimm JW, Buse C, Manaois M, Osincup D, Fyall A, Wells B (2006) Time-dependent dissociation of cocaine dose-response effects on sucrose craving and locomotion. Behav Pharmacol 17:143–149

    Article  CAS  PubMed  Google Scholar 

  • Grimm JW, Manaois M, Osincup D, Wells B, Buse C (2007) Naloxone attenuates incubated sucrose craving in rats. Psychopharmacology (Berl) 194:537–544

    Article  CAS  Google Scholar 

  • Grimm JW, Osincup D, Wells B, Manaois M, Fyall A, Buse C, Harkness JH (2008) Environmental enrichment attenuates cue-induced reinstatement of sucrose seeking in rats. Behav Pharmacol 19:777–785

    Article  PubMed  Google Scholar 

  • Hill AJ (2007) The psychology of food craving. Proc Nutr Soc 66:277–285

    Article  PubMed  Google Scholar 

  • Holland PC (2005) Amount of training effects in representation-mediated food aversion learning: no evidence of a role for associability changes. Learn Behav 33:464–478

    PubMed  Google Scholar 

  • Holland PC, Lasseter H, Agarwal I (2008) Amount of training and cue-evoked taste-reactivity responding in reinforcer devaluation. J Exp Psychol Anim Behav Process 34:119–132

    Article  PubMed  Google Scholar 

  • Johnson AW, Gallagher M, Holland PC (2009) The basolateral amygdala is critical to the expression of pavlovian and instrumental outcome-specific reinforcer devaluation effects. J Neurosci 29:696–704

    Article  CAS  PubMed  Google Scholar 

  • Kerfoot EC, Agarwal I, Lee HJ, Holland PC (2007) Control of appetitive and aversive taste-reactivity responses by an auditory conditioned stimulus in a devaluation task: a FOS and behavioral analysis. Learn Mem 14:581–589

    Article  PubMed  Google Scholar 

  • Kosten TR, Kosten TA, Poling J, Oliveto A (2005) “Incubation” of cocaine relapse during a disulfiram clinical trial college on problems of drug dependence annual meeting, poster #357

  • Li YQ, Li FQ, Wang XY, Wu P, Zhao M, Xu CM, Shaham Y, Lu L (2008) Central amygdala extracellular signal-regulated kinase signaling pathway is critical to incubation of opiate craving. J Neurosci 28:13248–13257

    Article  CAS  PubMed  Google Scholar 

  • Limebeer CL, Parker LA (2006) Effect of conditioning method and testing method on strength of lithium-induced taste aversion learning. Behav Neurosci 120:963–969

    Article  PubMed  Google Scholar 

  • Lu L, Hope BT, Dempsey J, Liu SY, Bossert JM, Shaham Y (2005) Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nat Neurosci 8:212–219

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Uejima JL, Gray SM, Bossert JM, Shaham Y (2007) Systemic and central amygdala injections of the mGluR(2/3) agonist LY379268 attenuate the expression of incubation of cocaine craving. Biol Psychiatry 61:591–598

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Wang X, Wu P, Xu C, Zhao M, Morales M, Harvey BK, Hoffer BJ, Shaham Y (2009) Role of ventral tegmental area glial cell line-derived neurotrophic factor in incubation of cocaine craving. Biol Psychiatry 66:137–145

    Article  CAS  PubMed  Google Scholar 

  • Mark GP, Weinberg JB, Rada PV, Hoebel BG (1995) Extracellular acetylcholine is increased in the nucleus accumbens following the presentation of an aversively conditioned taste stimulus. Brain Res 688:184–188

    Article  CAS  PubMed  Google Scholar 

  • Markou A, Weiss F, Gold LH, Caine SB, Schulteis G, Koob GF (1993) Animal models of drug craving. Psychopharmacology (Berl) 112:163–182

    Article  CAS  Google Scholar 

  • Nava F, Caldiroli E, Premi S, Lucchini A (2006) Relationship between plasma cortisol levels, withdrawal symptoms and craving in abstinent and treated heroin addicts. J Addict Dis 25:9–16

    Article  PubMed  Google Scholar 

  • Olesen OV, Schou M, Thomsen K (1976) Administration of lithium to rats by different routes. Neuropsychobiology 2:134–138

    Article  CAS  PubMed  Google Scholar 

  • Palmerino CC, Rusiniak KW, Garcia J (1980) Flavor-illness aversions: the peculiar roles of odor and taste in memory for poison. Science 208:753–755

    Article  CAS  PubMed  Google Scholar 

  • Parker LA (1998) Emetic drugs produce conditioned rejection reactions in the taste reactivity test. J Psychophysiol 12:3–13

    Google Scholar 

  • Phillips GD, Robbins TW, Everitt BJ (1994) Mesoaccumbens dopamine–opiate interactions in the control over behaviour by a conditioned reinforcer. Psychopharmacology (Berl) 114:345–359

    Article  CAS  Google Scholar 

  • Piasecki TM, Fiore MC, Baker TB (1998) Profiles in discouragement: two studies of variability in the time course of smoking withdrawal symptoms. J Abnorm Psychol 107:238–251

    Article  CAS  PubMed  Google Scholar 

  • Piasecki TM, Niaura R, Shadel WG, Abrams D, Goldstein M, Fiore MC, Baker TB (2000) Smoking withdrawal dynamics in unaided quitters. J Abnorm Psychol 109:74–86

    Article  CAS  PubMed  Google Scholar 

  • Pickens CL, Saddoris MP, Setlow B, Gallagher M, Holland PC, Schoenbaum G (2003) Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer devaluation task. J Neurosci 23:11078–11084

    CAS  PubMed  Google Scholar 

  • Ramirez-Lugo L, Nunez-Jaramillo L, Bermudez-Rattoni F (2007) Taste memory formation: role of nucleus accumbens. Chem Senses 32:93–97

    Article  CAS  PubMed  Google Scholar 

  • Reilly S, Bornovalova MA (2005) Conditioned taste aversion and amygdala lesions in the rat: a critical review. Neurosci Biobehav Rev 29:1067–1088

    Article  PubMed  Google Scholar 

  • Sclafani A, Azzara AV, Touzani K, Grigson PS, Norgren R (2001) Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats. Behav Neurosci 115:920–933

    Article  CAS  PubMed  Google Scholar 

  • Stalnaker TA, Takahashi Y, Roesch MR, Schoenbaum G (2009) Neural substrates of cognitive inflexibility after chronic cocaine exposure. Neuropharmacology 56(Suppl 1):63–72

    Article  CAS  PubMed  Google Scholar 

  • Tampier L, Quintanilla ME, Israel Y (2008) Tolerance to disulfiram induced by chronic alcohol intake in the rat. Alcohol Clin Exp Res 32:937–941

    Article  CAS  PubMed  Google Scholar 

  • Uejima JL, Bossert JM, Poles GC, Lu L (2007) Systemic and central amygdala injections of the mGluR2/3 agonist LY379268 attenuate the expression of incubation of sucrose craving in rats. Behav Brain Res 181:292–296

    Article  CAS  PubMed  Google Scholar 

  • Ventura R, Morrone C, Puglisi-Allegra S (2007) Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli. Proc Natl Acad Sci USA 104:5181–5186

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–560

    Article  CAS  PubMed  Google Scholar 

  • Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494

    Article  CAS  PubMed  Google Scholar 

  • Yasoshima Y, Morimoto T, Yamamoto T (2000) Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats. Brain Res 869:15–24

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Institute on Drug Abuse/National Institutes of Health grant R15 DA016285-02, the Western Washington University Biomedical Research Activities in Neuroscience Initiative, and the Western Washington University Foundation. The authors wish to thank Christine Ratliff, Kindsey North, Stefan Collins, Jesse Barnes, and Addison Tice for helping with data collection.

Author information

Authors and Affiliations

  1. Department of Psychology and Program in Behavioral Neuroscience, Western Washington University, 516 High Street, Bellingham, WA, 98225-9172, USA

    John H. Harkness, Sierra Webb & Jeffrey W. Grimm

Authors
  1. John H. Harkness
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sierra Webb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey W. Grimm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey W. Grimm.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harkness, J.H., Webb, S. & Grimm, J.W. Abstinence-dependent transfer of lithium chloride-induced sucrose aversion to a sucrose-paired cue in rats. Psychopharmacology 208, 521–530 (2010). https://doi.org/10.1007/s00213-009-1755-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1755-5

Keywords

Search

Navigation