Skip to main content
Log in

Choice between delayed food and immediate opioids in rats: treatment effects and individual differences

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

Abstract

Rationale

Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards.

Objectives and methods

To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food.

Results

Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions.

Conclusions

Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

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
Fig. 6

Similar content being viewed by others

References

  • American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edn. American Psychiatric Publishing, Arlington

    Book  Google Scholar 

  • Anokhin AP, Golosheykin S, Grant JD, Heath AC (2011) Heritability of delay discounting in adolescence: a longitudinal twin study. Behav Genet 41:175–183

    Article  PubMed  Google Scholar 

  • Anokhin AP, Grant JD, Mulligan RC, Heath AC (2015) The genetics of impulsivity: evidence for the heritability of delay discounting. Biol Psychiatry 77:887–894

    Article  PubMed  Google Scholar 

  • Bickel WK, Landes RD, Christensen DR, Jackson L, Jones BA, Kurth-Nelson Z, Redish AD (2011) Single- and cross-commodity discounting among cocaine addicts: the commodity and its temporal location determine discounting rate. Psychopharmacology 217:177–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bickel WK, Koffarnus MN, Moody L, Wilson AG (2014) The behavioral- and neuro-economic process of temporal discounting: a candidate behavioral marker of addiction. Neuropharmacology 76(Pt B):518–527

    Article  CAS  PubMed  Google Scholar 

  • Briggs SA, Hall BJ, Wells C, Slade S, Jaskowski P, Morrison M, Rezvani AH, Rose JE, Levin ED (2016) Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav 142:1–7

    Article  CAS  PubMed  Google Scholar 

  • Collins GT, Gerak LR, Javors MA, France CP (2016) Lorcaserin reduces the discriminative stimulus and reinforcing effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 356:85–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cousins V, Rose JE, Levin ED (2014) IV nicotine self-administration in rats using a consummatory operant licking response: sensitivity to serotonergic, glutaminergic and histaminergic drugs. Prog Neuro-Psychopharmacol Biol Psychiatry 54:200–205

    Article  CAS  Google Scholar 

  • Dugosh K, Abraham A, Seymour B, McLoyd K, Chalk M, Festinger D (2016) A systematic review on the use of psychosocial interventions in conjunction with medications for the treatment of opioid addiction. J Addict Med 10:93–103

    Article  PubMed  Google Scholar 

  • Evenden JL, Ryan CN (1996) The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128:161–170

    Article  CAS  PubMed  Google Scholar 

  • Gerak LR, Collins GT, France CP (2016) Effects of lorcaserin on cocaine and methamphetamine self-administration and reinstatement of responding previously maintained by cocaine in rhesus monkeys. J Pharmacol Exp Ther 359:383–391

    Article  CAS  PubMed  Google Scholar 

  • Hadamitzky M, Feja M, Becker T, Koch M (2009) Effects of acute systemic administration of serotonin2A/C receptor ligands in a delay-based decision-making task in rats. Behav Pharmacol 20:415–423

    Article  CAS  PubMed  Google Scholar 

  • Harvey-Lewis C, Li Z, Higgins GA, Fletcher PJ (2016) The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity. Neuropharmacology 101:237–245

    Article  CAS  PubMed  Google Scholar 

  • Heyman GM (2013) Addiction and choice: theory and new data. Front Psych 4:31

    Google Scholar 

  • Higgins GA, Silenieks LB, Rossmann A, Rizos Z, Noble K, Soko AD, Fletcher PJ (2012) The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control. Neuropsychopharmacology 37:1177–1191

    Article  CAS  PubMed  Google Scholar 

  • Higgins GA, Silenieks LB, Lau W, de Lannoy IA, Lee DK, Izhakova J, Coen K, Le AD, Fletcher PJ (2013) Evaluation of chemically diverse 5-HT(2)c receptor agonists on behaviours motivated by food and nicotine and on side effect profiles. Psychopharmacology 226:475–490

    Article  CAS  PubMed  Google Scholar 

  • Higgins GA, Silenieks LB, Altherr EB, MacMillan C, Fletcher PJ, Pratt WE (2016) Lorcaserin and CP-809101 reduce motor impulsivity and reinstatement of food seeking behavior in male rats: implications for understanding the anti-obesity property of 5-HT2C receptor agonists. Psychopharmacology 233:2841–2856

    Article  CAS  PubMed  Google Scholar 

  • Holtyn AF, Koffarnus MN, DeFulio A, Sigurdsson SO, Strain EC, Schwartz RP, Silverman K (2014) Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users. J Appl Behav Anal 47:681–693

    Article  PubMed  PubMed Central  Google Scholar 

  • Homberg JR (2012) Serotonin and decision making processes. Neurosci Biobehav Rev 36:218–236

    Article  CAS  PubMed  Google Scholar 

  • Huskinson SL, Woolverton WL, Green L, Myerson J, Freeman KB (2015) Delay discounting of food by rhesus monkeys: cocaine and food choice in isomorphic and allomorphic situations. Exp Clin Psychopharmacol 23:184–193

    Article  PubMed  PubMed Central  Google Scholar 

  • Lamb RJ, Maguire DR, Ginsburg BC, Pinkston JW, France CP (2016) Determinants of choice, and vulnerability and recovery in addiction. Behav Process 127:35–42

    Article  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Lenoir M, Cantin L, Vanhille N, Serre F, Ahmed SH (2013) Extended heroin access increases heroin choices over a potent nondrug alternative. Neuropsychopharmacology 38:1209–1220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levin ED, Johnson JE, Slade S, Wells C, Cauley M, Petro A, Rose JE (2011) Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats. J Pharmacol Exp Ther 338:890–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lussier JP, Heil SH, Mongeon JA, Badger GJ, Higgins ST (2006) A meta-analysis of voucher-based reinforcement therapy for substance use disorders. Addiction 101:192–203

    Article  PubMed  Google Scholar 

  • Maguire DR, Gerak LR, France CP (2013) Delay discounting of food and remifentanil in rhesus monkeys. Psychopharmacology 229:323–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maguire DR, Gerak LR, France CP (2016) Delay discounting of the mu-opioid receptor agonist remifentanil in rhesus monkeys. Behav Pharmacol 27:148–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazur JE (1987) An adjusting procedure for studying delayed reinforcement. In: Commons ML, Mazur JE, Nevin JA, Rachlin H (eds) Quantitative analyses of behavior, vol 5: The effect of delay and of intervening events on reinforcement value. Earlbaum, Hillsdale, pp 55–73

  • Mobini S, Chiang TJ, Al-Ruwaitea AS, Ho MY, Bradshaw CM, Szabadi E (2000) Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis. Psychopharmacology 149:313–318

    Article  CAS  PubMed  Google Scholar 

  • Myerson J, Green L, Scott Hanson J, Holt DD, Estle SJ (2003) Discounting delayed and probabilistic rewards: processes and traits. J Econ Psychol 24:619–635

    Article  Google Scholar 

  • National Research Council (2011) Guidelines for the care and use of mammals in neuroscience and behavioral research. National Academies Press, Washington DC

    Google Scholar 

  • Navarra R, Comery TA, Graf R, Rosenzweig-Lipson S, Day M (2008) The 5-HT(2C) receptor agonist WAY-163909 decreases impulsivity in the 5-choice serial reaction time test. Behav Brain Res 188:412–415

    Article  CAS  PubMed  Google Scholar 

  • Neelakantan H, Holliday ED, Fox RG, Stutz SJ, Comer SD, Haney M, Anastasio NC, Moeller FG, Cunningham KA (2017) Lorcaserin suppresses oxycodone self-administration and relapse vulnerability in rats. ACS Chem Neurosci 8:1065–1073

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Odum AL (2011) Delay discounting: trait variable? Behav Process 87:1–9

    Article  Google Scholar 

  • Panlilio LV, Schindler CW (2000) Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats. Psychopharmacology 150:61–66

    Article  CAS  PubMed  Google Scholar 

  • Panlilio LV, Katz JL, Pickens RW, Schindler CW (2003) Variability of drug self-administration in rats. Psychopharmacology 167:9–19

    Article  CAS  PubMed  Google Scholar 

  • Panlilio LV, Thorndike EB, Schindler CW (2008) A stimulus-control account of regulated drug intake in rats. Psychopharmacology 196:441–450

    Article  CAS  PubMed  Google Scholar 

  • Peterson JR, Hill CC, Kirkpatrick K (2015) Measurement of impulsive choice in rats: same- and alternate-form test-retest reliability and temporal tracking. J Exp Anal Behav 103:166–179

    Article  PubMed  Google Scholar 

  • Platt ML, Watson KK, Hayden BY, Shepherd SV, Klein JT (2010) Frontiers in Neuroscience Neuroeconomics: implications for understanding the neurobiology of addiction. In: Kuhn CM, Koob GF (eds) Advances in the neuroscience of addiction. CRC Press/Taylor & Francis Llc., Boca Raton

    Google Scholar 

  • Renda CR, Madden GJ (2016) Impulsive choice and pre-exposure to delays: III. Four-month test-retest outcomes in male wistar rats. Behav Process 126:108–112

    Article  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 

  • Roberts DC, Gabriele A, Zimmer BA (2013) Conflation of cocaine seeking and cocaine taking responses in IV self-administration experiments in rats: methodological and interpretational considerations. Neurosci Biobehav Rev 37:2026–2036

    Article  CAS  PubMed  Google Scholar 

  • Sawilowsky SS (2009) New effect size rules of thumb. J Mod Appl Stat Methods 8:597–599

    Article  Google Scholar 

  • Secci ME, Factor JA, Schindler CW, Panlilio LV (2016) Choice between delayed food and immediate oxycodone in rats. Psychopharmacology 233:3977–3989

    Article  CAS  PubMed  Google Scholar 

  • Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Dosa PI, Covel JA, Ren A, Webb RR, Beeley NR, Martin M, Morgan M, Espitia S, Saldana HR, Bjenning C, Whelan KT, Grottick AJ, Menzaghi F, Thomsen WJ (2008) Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem 51:305–313

    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 

  • Stein JS, Renda CR, Barker SM, Liston KJ, Shahan TA, Madden GJ (2015) Impulsive choice predicts anxiety-like behavior, but not alcohol or sucrose consumption, in male Long-Evans rats. Alcohol Clin Exp Res 39:932–940

    Article  PubMed  Google Scholar 

  • Talpos JC, Wilkinson LS, Robbins TW (2006) A comparison of multiple 5-HT receptors in two tasks measuring impulsivity. J Psychopharmacol 20:47–58

    Article  CAS  PubMed  Google Scholar 

  • Woolverton WL, Anderson KG (2006) Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys. Psychopharmacology 186:99–106

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Pang G, Zhang YM, Li G, Xu S, Dong L, Stackman RW Jr, Zhang G (2015) Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Neurosci Lett 607:23–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang G, Wu X, Zhang YM, Liu H, Jiang Q, Pang G, Tao X, Dong L, Stackman RW Jr (2016) Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice. Neuropharmacology 101:246–254

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. The authors declare no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leigh V. Panlilio.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Panlilio, L.V., Secci, M.E., Schindler, C.W. et al. Choice between delayed food and immediate opioids in rats: treatment effects and individual differences. Psychopharmacology 234, 3361–3373 (2017). https://doi.org/10.1007/s00213-017-4726-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4726-2

Keywords

Navigation