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.
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References
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edn. American Psychiatric Publishing, Arlington
Anokhin AP, Golosheykin S, Grant JD, Heath AC (2011) Heritability of delay discounting in adolescence: a longitudinal twin study. Behav Genet 41:175–183
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
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
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
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
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
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
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
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
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
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
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
Heyman GM (2013) Addiction and choice: theory and new data. Front Psych 4:31
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
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
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
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
Homberg JR (2012) Serotonin and decision making processes. Neurosci Biobehav Rev 36:218–236
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
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
Lenoir M, Ahmed SH (2008) Supply of a nondrug substitute reduces escalated heroin consumption. Neuropsychopharmacology 33:2272–2282
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
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
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
Maguire DR, Gerak LR, France CP (2013) Delay discounting of food and remifentanil in rhesus monkeys. Psychopharmacology 229:323–330
Maguire DR, Gerak LR, France CP (2016) Delay discounting of the mu-opioid receptor agonist remifentanil in rhesus monkeys. Behav Pharmacol 27:148–154
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
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
National Research Council (2011) Guidelines for the care and use of mammals in neuroscience and behavioral research. National Academies Press, Washington DC
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
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
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
Odum AL (2011) Delay discounting: trait variable? Behav Process 87:1–9
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
Panlilio LV, Katz JL, Pickens RW, Schindler CW (2003) Variability of drug self-administration in rats. Psychopharmacology 167:9–19
Panlilio LV, Thorndike EB, Schindler CW (2008) A stimulus-control account of regulated drug intake in rats. Psychopharmacology 196:441–450
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
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
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
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
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
Sawilowsky SS (2009) New effect size rules of thumb. J Mod Appl Stat Methods 8:597–599
Secci ME, Factor JA, Schindler CW, Panlilio LV (2016) Choice between delayed food and immediate oxycodone in rats. Psychopharmacology 233:3977–3989
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
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
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
Talpos JC, Wilkinson LS, Robbins TW (2006) A comparison of multiple 5-HT receptors in two tasks measuring impulsivity. J Psychopharmacol 20:47–58
Woolverton WL, Anderson KG (2006) Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys. Psychopharmacology 186:99–106
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
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
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.
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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
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DOI: https://doi.org/10.1007/s00213-017-4726-2