Abstract
Rationale
Cue-induced craving precedes drug relapse and contributes to eating disorders. Opiate antagonists have been demonstrated to be effective at reducing cravings for drugs and food. Craving, as defined as responding for a stimulus previously associated with a reward, increases, or incubates, over forced abstinence in an animal model of relapse.
Objectives
This paper aims to determine anticraving effects of the opiate antagonist, naloxone, on the incubation of sucrose craving.
Methods
106 male Long-Evans rats lever pressed for 10% sucrose solution 2 h/day for 10 days. On either day 1 or 30 of forced abstinence, rats responded in extinction for 6 h and then were injected (ip) with either saline or naloxone (0.001, 0.01, 0.1, 1, or 10 mg/kg). The rats then responded for 1 h for presentation of a tone + light cue previously presented with every sucrose delivery during self-administration training.
Results
The rats responded more in extinction and following saline on day 30 vs day 1 (an incubation of craving). Except for a trend for a decrease in responding following 10 mg/kg on day 1, naloxone was primarily effective on day 30. On day 30, naloxone significantly reduced responding at all doses except for 0.1 mg/kg.
Conclusions
The time-dependent increase in sensitivity to an opiate antagonist is consistent with time-dependent changes in the opiate system following forced abstinence from sucrose. These changes may partly underlie the incubation of sucrose craving. In addition, these findings could be used to support the use of naloxone as an anticraving medication in protracted abstinence.
Similar content being viewed by others
References
Bossert JM, Ghitza UE, Lu L, Epstein DH, Shaham Y (2005) Neurobiology of relapse to heroin and cocaine seeking: an update and clinical implications. Eur J Pharmacol 526:36–50
Burattini C, Burbassi S, Aicardi G, Cervo L (2007) Effects of naltrexone on cocaine- and sucrose-seeking behaviour in response to associated stimuli in rats. Int J Neuropsychopharmacol:1–7 (in press)
Centers for Disease Control and Prevention (CDC) (2007, February) Overweight and obesity: Trends. Retrieved April 18, 2007, from Centers for Disease Control and Prevention: http://www.cdc.gov/nccdphp/dnpa/obesity/trend/index.htm
Ciccocioppo R, Martin-Fardon R, Weiss F (2002) Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 27:391–399
Colantuoni C, Schwenker J, McCarthy J, Rada P, Ladenheim B, Cadet JL, Schwartz GJ, Moran TH, Hoebel BG (2001) Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport 12:3549–3552
Colantuoni C, Rada P, McCarthy J, Patten C, Avena NM, Chadeayne A, Hoebel BG (2002) Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obes Res 10:478–488
Crombag HS, Gorny G, Li Y, Kolb B, Robinson TE (2005) Opposite effects of amphetamine self-administration experience on dendritic spines in the medial and orbital prefrontal cortex. Cereb Cortex 15:341–348
D’Anci KE, Kanarek RB (2004) Naltrexone antagonism of morphine antinociception in sucrose- and chow-fed rats. Nutr Neurosci 7:57–61
Devine DP, Leone P, Pocock D, Wise RA (1993) Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies. J Pharmacol Exp Ther 266:1236–1246
Drewnowski A, Krahn DD, Demitrack MA, Nairn K, Gosnell BA (1995) Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am J Clin Nutr 61:1206–1212
Epstein AM, King AC (2004) Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav 77:29–37
Glass MJ, O’Hare E, Cleary JP, Billington CJ, Levine AS (1999) The effect of naloxone on food-motivated behavior in the obese Zucker rat. Psychopharmacology (Berl) 141:378–384
Gonzalez FA, Goldberg SR (1977) Effects of cocaine and d-amphetamine on behavior maintained under various schedules of food presentation in squirrel monkeys. J Pharmacol Exp Ther 201:33–43
Grimm JW, Fyall AM, Osincup DP (2005) Incubation of sucrose craving: effects of reduced training and sucrose pre-loading. Physiol Behav 84:73–79
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
Grodstein F, Levine R, Troy L, Spencer T, Colditz GA, Stampfer MJ (1996) Three-year follow-up of participants in a commercial weight loss program. Can you keep it off? Arch Intern Med 156:1302–1306
Holland PC, Bouton ME (1999) Hippocampus and context in classical conditioning. Curr Opin Neurobiol 9:195–202
Julien RM (2001) A primer of drug action: A concise, non-technical guide to the actions, uses, and side effects of psychoactive drugs (9th ed.). Worth Publishers, New York
Leri F, Burns LH (2005) Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats. Pharmacol Biochem Behav 82:252–262
Lu L, Dempsey J (2004) Cocaine seeking over extended withdrawal periods in rats: time dependent increases of responding induced by heroin priming over the first 3 months. Psychopharmacology (Berl) 176:109–114
Lu L, Grimm JW, Hope BT, Shaham Y (2004) Incubation of cocaine craving after withdrawal: a review of preclinical data. Neuropharmacology 47:214–226
MacDonald AF, Billington CJ, Levine AS (2003) Effects of the opioid antagonist naltrexone on feeding induced by DAMGO in the ventral tegmental area and in the nucleus accumbens shell region in the rat. Am J Physiol Regul Integr Comp Physiol 285:R999–R1004
Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1987) Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci 7:2445–2464
Marrazzi MA, Markham KM, Kinzie J, Luby ED (1995) Binge eating disorder: response to naltrexone. Int J Obes Relat Metab Disord 19:143–145
McBride WJ, Chernet E, McKinzie DL, Lumeng L, Li TK (1998) Quantitative autoradiography of mu-opioid receptors in the CNS of alcohol-naive alcohol-preferring P and -nonpreferring NP rats. Alcohol 16:317–323
O’Brien CP (2003) Research advances in the understanding and treatment of addiction. Am J Addict 12 Suppl 2:S36–47
Olmstead MC, Burns LH (2005) Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats. Psychopharmacology (Berl) 181:576–581
O’Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek MJ (2002) Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology (Berl) 160:19–29
Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285
Phillips G, Willner P, Sampson D, Nunn J, Muscat R (1991) Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine. Psychopharmacology (Berl) 104:125–131
Pickering C, Liljequist S (2003) Cue-induced behavioural activation: a novel model of alcohol craving? Psychopharmacology (Berl) 168:307–313
Powell KJ, Abul-Husn NS, Jhamandas A, Olmstead MC, Beninger RJ, Jhamandas K (2002) Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats. J Pharmacol Exp Ther 300:588–596
Reid LD (1985) Endogenous opioid peptides and regulation of drinking and feeding. Am J Clin Nutr 42:1099–1132
Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42
Sobik L, Hutchison K, Craighead L (2005) Cue-elicited craving for food: a fresh approach to the study of binge eating. Appetite 44:253–261
Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A 89:2046–2050
Uejima JL, Bossert JM, Poles GC, Lu L (2007) Systemic and central amygdala injections of the mGluR(2/3) agonist LY379268 attenuate the expression of incubation of sucrose craving in rats. Behav Brain Res (May 1, Epub ahead of print)
Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–560
Zhang M, Kelley AE (1997) Opiate agonists microinjected into the nucleus accumbens enhance sucrose drinking in rats. Psychopharmacology (Berl) 132:350–360
Acknowledgement
This research was supported by NIDA/NIH grant DA016285-01 and an underrepresented minority student supplement award (DA016285-01-S2).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Grimm, J.W., Manaois, M., Osincup, D. et al. Naloxone attenuates incubated sucrose craving in rats. Psychopharmacology 194, 537–544 (2007). https://doi.org/10.1007/s00213-007-0868-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-007-0868-y