Abstract
Alcohol (EtOH) addiction can be characterized as a chronic relapsing disorder. EtOH craving is a critical precipitating factor to relapse. Environmental and conditioning cues can elicit drug-seeking ‘craving’ in both humans and rodents. The operant Pavlovian Spontaneous Recovery (PSR) model of EtOH-seeking is a unique and suitable model for studying ‘craving-like’ behavior as well as examining underlying neural systems and mechanisms that may be involved in ‘craving-like’ and, by extension, relapse behavior in rodents. Our objective is to provide the reader with details and methods on the benefits of using the PSR model to examine and better understand EtOH ‘craving-like’ behavior.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ferri M, Amato L, Davoli M (2006) Alcoholics anonymous and other 12-step programmes for alcohol dependence. Cochrane Database Syst Rev 3:CD005032
Gawin FH, Kleber HD (1986) Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations. Arch Gen Psychiatry 43:107–113
O’Brien CP, Childress AR, Ehrman R, Robbins SJ (1998) Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol 12(1):15–22
Li P, Wu P, **n X, Fan YL, Wang GB, Wang F, Ma MY, Xue MM, Luo YX, Yang FD, Bao YP, Shi J, Sun HQ, Lu L (2015) Incubation of alcohol craving during abstinence in patients with alcohol dependence. Addict Biol 20:513–522
Gordon SM, Sterling R, Siatkowski C, Raively K, Weinstein S, Hill PC (2006) Inpatient desire to drink as a predictor of relapse to alcohol use following treatment. Am J Addict 15:242–245
Pavlov IP (1927) Conditioned reflexes (G.V. Anrep, trans). Oxford University Press, London
Rodd ZA, Bell RL, Sable HJ, Murphy JM, McBride WJ (2004) Recent advances in animal models of alcohol craving and relapse. Pharmacol Biochem Behav 79(3):439–450
Martin-Fardon R, Weiss F (2013) Modeling relapse in animals. Curr Top Behav Neurosci 13:403–432
DiCiano P, Everitt BJ (2002) Reinstatement and spontaneous recovery of cocaine-seeking following extinction and different durations of withdrawal. Behav Pharmacol 13:397–405
Widholm JJ (2010) Extinction learning as a model of drug treatment and relapse: a behavioral overview. Open Addict J 3:57–62
Franken IH, de Haan HA, van der Meer CW, Haffmans PM, Hendriks VM (1999) Cue reactivity and effects of cue exposure in abstinent posttreatment drug users. J Subst Abus Treat 16(1):81–85
Cunningham CL, Fidler TL, Hill KG (2000) Animal models of alcohol's motivational effects. Alcohol Res Health 24(2):85–92
Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology 189(1):1–16
Leeman RF, Heilig M, Cunningham CL, Stephens DN, Duka T, O’Malley SS (2010) Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes. Addict Biol 15(2):109–124
Samson HH (2000) The microstructure of ethanol drinking: genetic and behavioral factors in control of drinking patterns. Addiction 95(Suppl 2):S61–S72
Samson HH, Czachowski CL (2003) Behavioral measures of alcohol self-administration and intake control: rodent models. Int Rev Neurobiol 54:107–143
Lê AD, Funk D, Harding S, Juzytsch W, Fletcher PJ, Shaham Y (2006) Effects of dexfenfluramine and 5-HT3 receptor antagonists on stress-induced reinstatement of alcohol seeking in rats. Psychopharmacology 186(1):82–92
de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75(2):134–143
de Wit H, Stewart J (1983) Drug reinstatement of heroin-reinforced responding in the rat. Psychopharmacology 79(1):29–31
Shaham Y, Adamson LK, Grocki S, Corrigall WA (1997) Reinstatement and spontaneous recovery of nicotine seeking in rats. Psychopharmacology 130(4):396–403
Lê AD, Quan B, Juzytch W, Fletcher PJ, Joharchi N, Shaham Y (1998) Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats. Psychopharmacology 135(2):169–174
Richards JK, Simms JA, Steensland P, Taha SA, Borgland SL, Bonci A, Bartlett SE (2008) Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats. Psychopharmacology 199(1):109–117
Kleber H, Gawin F (1986) Psychopharmacological trials in cocaine abuse treatment. Am J Drug Alcohol Abuse 12(3):235–246
Pickens CL, Airavaara M, Theberge F, Fanous S, Hope BT, Shaham Y (2011) Neurobiology of the incubation of drug craving. Trends Neurosci 34(8):411–420
Bouton ME, Bolles RC (1979) Role of conditioned contextual stimuli in reinstatement of extinguished fear. J Exp Psychol Anim Behav Process 5(4):368–378
Hamlin AS, Newby J, McNally GP (2007) The neural correlates and role of D1 dopamine receptors in renewal of extinguished alcohol-seeking. Neuroscience 146(2):525–536
Hamlin AS, Clemens KJ, McNally GP (2008) Renewal of extinguished cocaine-seeking. Neuroscience 151(3):659–670
Chaudhri N, Sahuque LL, Janak PH (2009) Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats. Psychopharmacology 207:303–314
Chaudhri N, Sahuque LL, Schairer WW, Janak PH (2010) Separable roles of the nucleus accumbens core and shell in context- and cue-induced alcohol-seeking. Neuropsychopharmacology 35:783–791
Katner SN, Magalong JG, Weiss F (1999) Reinstatement of alcohol-seeking behavior by drug-associated discriminative stimuli after prolonged extinction in the rat. Neuropsychopharmacology 20(5):471–479
Katner SN, Weiss F (1999) Ethanol-associated olfactory stimuli reinstate ethanol-seeking behavior after extinction and modify extracellular dopamine levels in the nucleus accumbens. Alcohol Clin Exp Res 23(11):1751–1760
Macintosh JJ (1977) Stimulus control: attentional factors. In: Honig WK, Staddon JER (eds) Handbook on Operant Behavior. Prentice-Hall, Englewood Cliffs, pp 162–241
Robbins SJ (1990) Mechanisms underlying spontaneous recovery in authosha**. J Exp Psychol Anim Behav Processes 16:235–249
Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li TK (2002) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure. Alcohol Clin Exp Res 26(11):1632–1641
Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li TK (2002) Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol- preferring (P) rats: II. Adult exposure. Alcohol Clin Exp Res 26(11):1642–1652
Getachew B, Hauser SR, Dhaher R, Katner SN, Bell RL, Oster SM, McBride WJ, Rodd ZA (2011) CB1 receptors regulate alcohol-seeking behavior and alcohol self-administration of alcohol-preferring (P) rats. Pharmacol Biochem Behav 97(4):669–675
Dhaher R, Hauser SR, Getachew B, Bell RL, McBride WJ, McKinzie DL, Rodd ZA (2010) The Orexin-1 receptor antagonist SB-334867 reduces alcohol relapse drinking, but not alcohol-seeking, in alcohol-preferring (P) rats. J Addict Med 4(3):153–159
Dhaher R, Toalston JE, Hauser SR, Bell RL, McKinzie DL, McBride WJ, Rodd ZA (2012) Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Alcohol 46(1):17–27
Knight CP, Hauser SR, Deehan GA Jr, Toalston JE, McBride WJ, Rodd ZA (2016) Oral conditioned cues can enhance or inhibit ethanol (EtOH)-seeking and EtOH-relapse drinking by alcohol-preferring (P) rats. Alcohol Clin Exp Res 40(4):906–915
Hauser SR, Ding ZM, Getachew B, Toalston JE, Oster SM, McBride WJ, Rodd ZA (2011) The posterior ventral tegmental area mediates alcohol-seeking behavior in alcohol-preferring rats. J Pharmacol Exp Ther 336(3):857–865
Hauser SR, Deehan GA Jr, Toalston JE, Bell RL, McBride WJ, Rodd ZA (2014) Enhance alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors. Psychopharmacology 231(18):3745–3755
Hauser SR, Deehan GA Jr, Dhaher R, Knight CP, Wilden JA, McBride WJ, Rodd ZA (2015) D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats. Neuroscience 295:243–251
Hauser SR, Deehan GA Jr, Knight CP, Waeiss RA, Truitt WA, Johnson PL, Bell RL, McBride WJ, Rodd ZA (2019) Conditioned stimuli affect ethanol-seeking by female alcohol-preferring (P) rats: the role of repeated-deprivations, cue-pretreatment, and cue-temporal intervals. Psychopharmacology 236(9):2835–2846
LeCocq MR, Lahlou S, Chahine M, Padillo LN, Chaudhri N (2018) Modeling relapse to Pavlovian alcohol-seeking in rats using reinstatement and spontaneous recovery paradigms. Alcohol Clin Exp Res 42(9):1795–1806
Anton RF (1999) What is craving? Models and implications for treatment. Alcohol Res Health 23(3):165–173
Rodd ZA, Anstrom KK, Knapp DJ, Racz I, Zimmer A, Serra S, Bell RL, Woodward DJ, Breese GR, Colombo G (2005) Factors mediating alcohol craving and relapse: stress, compulsivity, and genetics. Alcohol Clin Exp Res 29(7):1325–1333
Hauser SR, Deehan GA Jr, Knight CP, Toalston JE, McBride WJ, Rodd ZA (2016) Parameters of context-induced ethanol (EtOH)-seeking in alcohol-preferring (P) rats: temporal analysis, effects of repeated deprivation, and EtOH priming injections. Alcohol Clin Exp Res 40(10):2229–2239
Rodd ZA, McKinzie DL, Bell RL, McQueen VK, Murphy JM, Schoepp DD, McBride WJ (2006) The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. Behav Brain Res 171(2):207–215
Deehan GA Jr, McKinzie DL, Carroll FI, McBride WJ, Rodd ZA (2012) The long-lasting effects of JDTic, a kappa opioid receptor antagonist, on the expression of ethanol-seeking behavior and the relapse drinking of female alcohol-preferring (P) rats. Pharmacol Biochem Behav 101(4):581–587
Hauser SR, Waeiss RA, Molosh AI, Deehan GA Jr, Bell RL, McBride WJ, Rodd ZA (2020) Atrial natriuretic peptide (ANP): a novel mechanism for reducing ethanol consumption and seeking behaviors in female alcohol preferring (P) rats. Peptides 134:170403
Bell RL, Hauser S, Rodd ZA, Liang T, Sari Y, McClintick J, Rahman S, Engleman EA (2016) A genetic animal model of alcoholism for screening medications to treat addiction. Int Rev Neurobiol 126:179–261
Domi E, Domi A, Adermark L, Heilig M, Augier E (2021) Neurobiology of alcohol seeking behavior. J Neurochem 157(5):1585–1614
Funk D, Mak D, Coen K, Lê AD (2022) Role of alpha-2 adrenergic and kappa opioid receptors in the effects of alcohol gavage-induced dependence on alcohol seeking. Behav Brain Res 434:114032
Nelson BS, Fulenwider HD, Nennig SE, Smith BM, Sequeira MK, Chimberoff SH, Richie CT, Cheng K, Rice KC, Harvey BK, Heilig M, Schank JR (2019) Escalated alcohol self-administration and sensitivity to yohimbine-induced reinstatement in alcohol preferring rats: potential role of neurokinin-1 receptors in the amygdala. Neuroscience 413:77–85
Samson H, Files F, Brice G (1996) Patterns of ethanol consumption in a continuous access situation: the effect of adding a sweetener to the ethanol solution. Alcohol Clin Exp Res 20(1):101–109
Sanchis-Segura C, Spanagel R (2006) Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 11(1):2–38
Augier E, Flanigan M, Dulman RS, Pincus A, Schank JR, Rice KC, Kejun C, Heilig M, Tapocik JD (2014) Wistar rats acquire and maintain self-administration of 20% ethanol without water deprivation, saccharin/sucrose fading, or extended access training. Psychopharmacology 231(23):4561–4568
Hauser SR, Getachew B, Oster SM, Dhaher R, Ding ZM, Bell RL, McBride WJ, Rodd ZA (2012) Nicotine modulates alcohol-seeking and relapse by alcohol-preferring (P) rats in a time-dependent manner. Alcohol Clin Exp Res 36(1):43–54
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Academic Press, New York
Rosenthal MZ, Kutlu MG (2014) Translation of associative learning models into extinction reminders delivered via mobile phones during cue exposure interventions for substance use. Psychol Addict Behav 28(3):863–871
Willcocks AL, McNally GP (2014) An extinction retrieval cue attenuates renewal but not reacquisition of alcohol seeking. Behav Neurosci 128:83–91
McNally GP (2014) Extinction of drug seeking: neural circuits and approaches to augmentation. Neuropharmacology 76(Pt B):528–532
Rich MT, Abbott TB, Chung L, Gulcicek EE, Stone KL, Colangelo CM, Lam TT, Nairn AC, Taylor JR, Torregrossa MM (2016) Phosphoproteomic analysis reveals a novel mechanism of CaMKIIα regulation inversely induced by cocaine memory extinction versus reconsolidation. J Neurosci 36:7613–7627
Rich MT, Huang YH, Torregrossa MM (2019) Plasticity at Thalamo-amygdala synapses regulates cocaine-cue memory formation and extinction. Cell Rep 26:1010–1020.e5
Torregrossa MM, Gordon J, Taylor JR (2013) Double dissociation between the anterior cingulate cortex and nucleus accumbens core in encoding the context versus the content of pavlovian cocaine cue extinction. J Neurosci 33:8370–8377
Bender BN, Torregrossa MM (2021) Dorsolateral striatum dopamine-dependent cocaine seeking is resistant to Pavlovian cue extinction in male and female rats. Neuropharmacology 182:108403
Hauser SR, Deehan GA Jr, Knight CP, Waeiss RA, Engleman EA, Ding ZM, Johnson PL, McBride WJ, Truitt WA, Rodd ZA (2023) Inhibitory and excitatory alcohol-seeking cues distinct roles in behavior neurochemistry and mesolimbic pathway in alcohol preferring (P) rats. Drug and Alcohol Dependence 246:109858
Acknowledgements
Preparation of this manuscript and its associated experiments were supported in part by AA020908 (ZAR), AA013522 (RLB), AA022287, AA007611, AA007462, and AA010721. The views expressed in this manuscript do not necessarily represent those of the National Institutes of Health (NIH) or the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The products mentioned in this manuscript do not represent an endorsement of the particular manufacturer, but only reflect the products used by our laboratories. All authors claim no perceived or real conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Hauser, S.R., Bell, R.L., Rodd, Z.A. (2023). Pavlovian Spontaneous Recovery as a Measure of Alcohol-Seeking Behavior. In: Cyders, M.A. (eds) Translational Research Methods for Alcohol Use Disorders. Neuromethods, vol 201. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3267-3_2
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3267-3_2
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3266-6
Online ISBN: 978-1-0716-3267-3
eBook Packages: Springer Protocols