Skip to main content

Advertisement

Log in

Place conditioning in humans: opportunities for translational research

  • Theoretical and Methodological Perspective
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Translational research, especially research that bridges studies with humans and nonhuman species, is critical to advancing our understanding of human disorders such as addiction. This advancement requires reliable and rigorous models to study the underlying constructs contributing to the maladaptive behavior.

Objective

In this commentary, we address some of the challenges of conducting translational research by examining a single procedure, place conditioning. Place conditioning is commonly used with laboratory animals to study the conditioned rewarding effects of drugs, and recent studies indicate that a similar procedure can be used in humans.

Results

We discuss the opportunities and challenges of making the procedure comparable across species, as well as discuss the benefits of more systematically applying the procedure to humans.

Conclusion

We argue that the capacity of humans to report verbally on their internal experiences (perceptions, affective states, likes and dislikes) add an important dimension to the understanding of the procedures used in laboratory animals.

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

Similar content being viewed by others

References 

  • Aapro MS, Molassiotis A, Olver I (2005) Anticipatory nausea and vomiting. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer 13(2):117–121

    Article  PubMed  Google Scholar 

  • Astur RS, Carew AW, Deaton BE (2014) Conditioned place preferences in humans using virtual reality. Behav Brain Res 267:173–177

    Article  PubMed  Google Scholar 

  • Astur RS, Palmisano AN, Hudd EC, Carew AW, Deaton BE, Kuhney FS, Niezrecki RN, Santos M (2015) Pavlovian conditioning to food reward as a function of eating disorder risk. Behav Brain Res 291:277–282

    Article  PubMed  Google Scholar 

  • Astur RS, Palmisano AN, Carew AW, Deaton BE, Kuhney FS, Niezrecki RN, Hudd EC, Mendicino KL, Ritter CJ (2016) Conditioned place preferences in humans using secondary reinforcers. Behav Brain Res 297:15–19

    Article  PubMed  Google Scholar 

  • Ayres JJB, Philbin D, Cassidy S, Bellino L, Redlinger E (1992) Some parameters of latent inhibition. Learn Motiv 23(3):269–287

    Article  Google Scholar 

  • Banz BC, Worhunsky PD, Pittman BP, Astur RS, Tennen HA, Raskin SA, Austad CS, Wood RM, Fallahi CR, Potenza MN, Pearlson GD (2019) Relationships between drinking quantity and frequency and behavioral and hippocampal BOLD responses during working memory performance involving allocentric spatial navigation in college students. Drug Alcohol Depend 201:236–243

    Article  PubMed  PubMed Central  Google Scholar 

  • Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology 153(1):31–43

    Article  CAS  PubMed  Google Scholar 

  • Bardo MT, Neisewander JL (1986) Single-trial conditioned place preference using intravenous morphine. Pharmacol Biochem Behav 25(5):1101–1105

    Article  CAS  PubMed  Google Scholar 

  • Bardo MT, Rowlett JK, Harris MJ (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19(1):39–51

    Article  CAS  PubMed  Google Scholar 

  • Baron D, Holland CM, Carlson K, Wolfrum E, Thompson BL (2020) Adapting social conditioned place preference for use in young children. Neurobiol Learn Mem 172:107235

    Article  PubMed  Google Scholar 

  • Bevins RA, Cunningham CL (2006) Place conditioning: a methodological analysis. In: Tasks and techniques: a sampling of methodologies for the investigation of animal learning, behavior, and cognition. Nova Science, Hauppauge, NY, pp 99–110

  • Bevins RA, Besheer J (2005) Novelty reward as a measure of anhedonia. Neurosci Biobehav Rev 29(4–5):707–714

    Article  PubMed  Google Scholar 

  • Biénkowski P, Kuca P, Kostowski W (1995) Conditioned place preference after prolonged pre-exposure to ethanol. Pol J Pharmacol 47(2):189–191

    PubMed  Google Scholar 

  • Cahill CM, Xue L, Grenier P, Magnussen C, Lecour S, Olmstead MC (2013) Changes in morphine reward in a model of neuropathic pain. Behav Pharmacol 24(3):207–213

    Article  CAS  PubMed  Google Scholar 

  • Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. The Neuropharmacological Basis of Reward 433:264–319

    Google Scholar 

  • Childs E, de Wit H (2009) Amphetamine-induced place preference in humans. Biol Psychiat 65(10):900–904

    Article  CAS  PubMed  Google Scholar 

  • Childs E, de Wit H (2013) Contextual conditioning enhances the psychostimulant and incentive properties of d-amphetamine in humans. Addict Biol 18(6):985–992

    Article  CAS  PubMed  Google Scholar 

  • Childs E, de Wit H (2016) Alcohol-induced place conditioning in moderate social drinkers. Addiction 111(12):2157–2165

    Article  PubMed  PubMed Central  Google Scholar 

  • Childs E, Astur RS, de Wit H (2017) Virtual reality conditioned place preference using monetary reward. Behav Brain Res 322(Pt A):110–114

    Article  PubMed  PubMed Central  Google Scholar 

  • Cunningham CL, Prather LK (1992) Conditioning trial duration affects ethanol-induced conditioned place preference in mice. Anim Learn Behav 20(2):187–194

    Article  Google Scholar 

  • Cunningham CL, Howard MA, Gill SJ, Rubinstein M, Low MJ, Grandy DK (2000) Ethanol-conditioned place preference is reduced in dopamine D2 receptor-deficient mice. Pharmacol Biochem Behav 67(4):693–699

    Article  CAS  PubMed  Google Scholar 

  • Cunningham CL, Gremel CM, Groblewski PA (2006) Drug-induced conditioned place preference and aversion in mice. Nat Protoc 1(4):1662–1670

    Article  CAS  PubMed  Google Scholar 

  • de Wit H, Uhlenhuth EH, Pierri J, Johanson CE (1987) Individual differences in behavioral and subjective responses to alcohol. Alcohol Clin Exp Res 11(1):52–59

    Article  PubMed  Google Scholar 

  • Erb SM, Parker LA (1994) Individual differences in novelty-induced activity do not predict strength of amphetamine-induced place conditioning. Pharmacol Biochem Behav 48(3):581–586

    Article  CAS  PubMed  Google Scholar 

  • Ettenberg A, Raven MA, Danluck DA, Necessary BD (1999) Evidence for opponent-process actions of intravenous cocaine. Pharmacol Biochem Behav 64(3):507–512

    Article  CAS  PubMed  Google Scholar 

  • Fleming AS, Korsmit M, Deller M (1994) Rat pups are potent reinforcers to the maternal animal: Effects of experience, parity, hormones, and dopamine function. Psychobiology 22(1):44–53

    Article  CAS  Google Scholar 

  • Folley BS, Astur R, Jagannathan K, Calhoun VD, Pearlson GD (2010) Anomalous neural circuit function in schizophrenia during a virtual Morris water task. Neuroimage 49(4):3373–3384

    Article  PubMed  Google Scholar 

  • Griffiths RR, Balster RL (1979) Opioids: similarity between evaluations of subjective effects and animal self-administration results. Clin Pharmacol Ther 25(5 Pt 1):611–617

    Article  CAS  PubMed  Google Scholar 

  • Ikemoto S, Donahue KM (2005) A five-minute, but not a fifteen-minute, conditioning trial duration induces conditioned place preference for cocaine administration into the olfactory tubercle. Synapse 56(1):57–59

    Article  CAS  PubMed  Google Scholar 

  • Itzhak Y, Roger-Sánchez C, Kelley JB, Anderson KL (2010) Discrimination between cocaine-associated context and cue in a modified conditioned place preference paradigm: role of the nNOS gene in cue conditioning. Int J Neuropsych / Official Scientific Journal of the Collegium InternaNeuropsychopharmacologicum 13(2):171–180

    Article  CAS  Google Scholar 

  • Jasinski DR (1991) History of abuse liability testing in humans. Br J Addict 86(12):1559–1562

    Article  CAS  PubMed  Google Scholar 

  • King T, Vera-Portocarrero L, Gutierrez T, Vanderah TW, Dussor G, Lai J, Fields HL, Porreca F (2009) Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 12(11):1364–1366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King A, Vena A, Hasin DS, deWit H, O’Connor SJ, Cao D (2021) Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder. Am J Psychiatry 178(6):560–571

    Article  PubMed  PubMed Central  Google Scholar 

  • Klebaur JE, Bardo MT (1999) Individual differences in novelty seeking on the playground maze predict amphetamine conditioned place preference. Pharmacol Biochem Behav 63(1):131–136

    Article  CAS  PubMed  Google Scholar 

  • Koek W (2016) Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice. Psychopharmacology 233(11):2015–2024

    Article  CAS  PubMed  Google Scholar 

  • Krishnan S, Heer C, Cherian C, Sheffield MEJ (2022) Reward expectation extinction restructures and degrades CA1 spatial maps through loss of a dopaminergic reward proximity signal. Nat Commun 13(1):6662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamb RJ, Preston KL, Schindler CW, Meisch RA, Davis F, Katz JL, Henningfield JE, Goldberg SR (1991) The reinforcing and subjective effects of morphine in post-addicts: a dose-response study. J Pharmacol Exp Ther 259(3):1165–1173

    CAS  PubMed  Google Scholar 

  • Lee AM, Calarco CA, McKee SA, Mineur YS, Picciotto MR (2020) Variability in nicotine conditioned place preference and stress-induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine. Genes Brain Behav 19(3):e12601

    Article  PubMed  Google Scholar 

  • Li J, Murray CH, Weafer J, de Wit H (2020) Subjective Effects of Alcohol Predict Alcohol Choice in Social Drinkers. Alcohol Clin Exp Res 44(12):2579–2587

    Article  PubMed  PubMed Central  Google Scholar 

  • Linhardt M, Kiser DP, Pauli P, Hilger K (2022) Approach and avoidance beyond verbal measures: A quantitative meta-analysis of human conditioned place preference studies. Behav Brain Res 426:113834

    Article  PubMed  Google Scholar 

  • Lutz JA, Childs E (2021) Alcohol conditioned contexts enhance positive subjective alcohol effects and consumption. Behav Proc 187:104340

    Article  Google Scholar 

  • Lynch WJ, Nicholson KL, Dance ME, Morgan RW, Foley PL (2010) Animal models of substance abuse and addiction: implications for science, animal welfare, and society. Comp Med 60(3):177–188

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mattson BJ, Williams S, Rosenblatt JS, Morrell JI (2001) Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav Neurosci 115(3):683–694

    Article  CAS  PubMed  Google Scholar 

  • Mayo LM, de Wit H (2016) Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers. J Stud Alcohol Drugs 77(2):317–326

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayo LM, Fraser D, Childs E, Momenan R, Hommer DW, de Wit H, Heilig M (2013) Intergenerational transmission of stress in humans. Neuropsychopharmacology 38(6):921–929

  • McKendrick G, Graziane NM (2020) Drug-Induced Conditioned Place Preference and Its Practical Use in Substance Use Disorder Research. Front Behav Neurosci 14:582147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKendrick G, Garrett H, Tanniru S, Ballard S, Sun D, Silberman Y, Grigson PS, Graziane NM (2020) A novel method to study reward-context associations and drug-seeking behaviors. J Neurosci Methods 343:108857

    Article  CAS  PubMed  Google Scholar 

  • Molet M, Billiet G, Bardo MT (2013) Conditioned place preference and aversion for music in a virtual reality environment. Behav Proc 92:31–35

    Article  Google Scholar 

  • Murray JE, Bevins RA (2010) Cannabinoid conditioned reward and aversion: behavioral and neural processes. ACS Chem Neurosci 1(4):265–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Napier TC, Herrold AA, de Wit H (2013) Using conditioned place preference to identify relapse prevention medications. Neurosci Biobehav Rev 37(9 Pt A):2081–2086

  • Navratilova E, Xie JY, King T, Porreca F (2013) Evaluation of reward from pain relief. Ann N Y Acad Sci 1282:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nentwig TB, Myers KP, Grisel JE (2017) Initial subjective reward to alcohol in Sprague-Dawley rats. Alcohol 58:19–22

    Article  CAS  PubMed  Google Scholar 

  • Palmisano AN, Hudd EC, McQuade CM, de Wit H, Astur RS (2018) The effects of nicotine on conditioning, extinction, and reinstatement in humans. Addict Behav 77:51–58

    Article  PubMed  Google Scholar 

  • Pavlov PI (2010) Conditioned reflexes: an investigation of the physiological activity of the cerebral cortex. Ann Neurosci 17(3):136–141. https://doi.org/10.5214/ans.0972-7531.1017309

    Article  PubMed  Google Scholar 

  • Radell ML, Myers CE, Beck KD, Moustafa AA, Allen MT (2016) The Personality Trait of Intolerance to Uncertainty Affects Behavior in a Novel Computer-Based Conditioned Place Preference Task. Front Psychol 7:1175

    Article  PubMed  PubMed Central  Google Scholar 

  • Reichel CM, Bevins RA (2008) Competition between the conditioned rewarding effects of cocaine and novelty. Behav Neurosci 122(1):140–150

    Article  PubMed  Google Scholar 

  • Reichel CM, Bevins RA (2010) Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval. Behav Neurosci 124(1):141–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rock EM, Sticht MA, Limebeer CL, Parker LA (2016) Cannabinoid Regulation of Acute and Anticipatory Nausea. Cannabis and Cannabinoid Research 1(1):113–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prus AJ, James JR, Rosecrans JA (2009) Conditioned place preference. In: Buccafusco JJ (ed) Methods of behavior analysis in neuroscience, 2nd edn. CRC Press/Taylor & Francis, Boca Raton, FL. Chapter 4. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5229/

  • Rossi NA, Reid LD (1976) Affective states associated with morphine injections. Physiol Psychol 4(3):269–274

    Article  Google Scholar 

  • Scherma M, Fattore L, Fratta W, Fadda P (2021) Conditioned Place Preference (CPP) in Rats: From Conditioning to Reinstatement Test. Methods Mol Biol 2201:221–229

    Article  CAS  PubMed  Google Scholar 

  • Seidman MH, Lau CE, Chen R, Falk JL (1992) Orally self-administered cocaine: reinforcing efficacy by the place preference method. Pharmacol Biochem Behav 43(1):235–241

    Article  CAS  PubMed  Google Scholar 

  • Seymour CM, Wagner JJ (2008) Simultaneous expression of cocaine-induced behavioral sensitization and conditioned place preference in individual rats. Brain Res 1213:57–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimosato K, Watanabe S (2003) Concurrent evaluation of locomotor response to novelty and propensity toward cocaine conditioned place preference in mice. J Neurosci Methods 128(1–2):103–110

    Article  CAS  PubMed  Google Scholar 

  • Shipman SL, Astur RS (2008) Factors affecting the hippocampal BOLD response during spatial memory. Behav Brain Res 187(2):433–441

    Article  PubMed  Google Scholar 

  • Shipman SL, Malison RT, Siegel S, Rizzo AA, Astur RS (2006) Cocaine Induced Place Preference in a Virtual Environment. In 2006 International Workshop on Virtual Rehabilitation. https://doi.org/10.1109/iwvr.2006.1707528

  • Siddiqi SH, Kording KP, Parvizi J, Fox MD (2022) Causal mapping of human brain function. Nat Rev Neurosci 23(6):361–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spragg SDS (1940) Morphine addiction in chimpanzees. Comparative Psychology Monographs 15:7

    Google Scholar 

  • Spyraki C, Fibiger HC, Phillips AG (1982) Attenuation by haloperidol of place preference conditioning using food reinforcement. Psychopharmacology 77(4):379–382

    Article  CAS  PubMed  Google Scholar 

  • Stephens DN, Crombag HS, Duka T (2013) The challenge of studying parallel behaviors in humans and animal models. Curr Top Behav Neurosci 13:611–645

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Toyoshima M, Ichitani Y, Yamada K (2020) Enhanced methamphetamine-induced conditioned place preference in risk-taking rats. Behav Brain Res 378:112299

    Article  CAS  PubMed  Google Scholar 

  • Tenk CM, Wilson H, Zhang Q, Pitchers KK, Coolen LM (2009) Sexual reward in male rats: effects of sexual experience on conditioned place preferences associated with ejaculation and intromissions. Horm Behav 55(1):93–97

    Article  PubMed  Google Scholar 

  • Thiel KJ, Okun AC, Neisewander JL (2008) Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats. Drug Alcohol Depend 96(3):202–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tzschentke TM (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog Neurobiol 56(6):613–672

    Article  CAS  PubMed  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12(3–4):227–462

    Article  CAS  PubMed  Google Scholar 

  • van den Akker K, Jansen A, Frentz F, Havermans RC (2013) Impulsivity makes more susceptible to overeating after contextual appetitive conditioning. Appetite 70:73–80

    Article  PubMed  Google Scholar 

  • Vanderschuren LJMJ, Ahmed SH (2013) Animal studies of addictive behavior. Cold Spring Harb Perspect Med 3(4):a011932

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Hedger K, Cavallo JS, Ruiz NA, de Wit H (2018) Conditioning nausea in a laboratory setting: A pilot study. In bioRxiv, p. 243121. https://doi.org/10.1101/243121

  • Venniro M, Banks ML, Heilig M, Epstein DH, Shaham Y (2020) Improving translation of animal models of addiction and relapse by reverse translation. Nat Rev Neurosci 21(11):625–643

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson JL, Bevins RA (2008) Intravenous nicotine conditions a place preference in rats using an unbiased design. Pharmacol Biochem Behav 88(3):256–264

    Article  CAS  PubMed  Google Scholar 

  • Williams SB, Arriaga M, Korgaonkar AA, Morón JA, Han EB (2019) Hippocampal Activity Dynamics During Contextual Reward Association in Virtual Reality Place Conditioning. In bioRxiv :545608. https://doi.org/10.1101/545608

  • Zarrindast M-R, Ebrahimi-Ghiri M, Rostami P, Rezayof A (2007) Repeated pre-exposure to morphine into the ventral pallidum enhances morphine-induced place preference: involvement of dopaminergic and opioidergic mechanisms. Behav Brain Res 181(1):35–41

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

SK was supported by T32DA043469, RAB was supported by GM130461 and DA046109 and HdW was supported by DA02812.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harriet de Wit.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article belongs to a Special Issue on Innovating translational models of affective disorders

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishnan, S., Bevins, R.A. & de Wit, H. Place conditioning in humans: opportunities for translational research. Psychopharmacology 240, 2221–2230 (2023). https://doi.org/10.1007/s00213-023-06316-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-023-06316-8

Keywords

Navigation