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Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice

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Abstract

Rationale

Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory.

Objectives

The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP).

Materials and methods

Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration.

Results

Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation.

Conclusions

Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

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References

  • Ameri A (1999) The effects of cannabinoids on the brain. Prog Neurobiol 58:315–348

    Article  PubMed  CAS  Google Scholar 

  • Anagnostaras SG, Gale GD, Fanselow MS (2001) Hippocampus and contextual fear conditioning: recent controversies and advances. Hippocampus 11:8–17

    Article  PubMed  CAS  Google Scholar 

  • Anggadiredja K, Nakamichi M, Hiranita T, Tanaka H, Shoyama Y, Watanabe S, Yamamoto T (2004) Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade. Neuropsychopharmacology 29:1470–1478

    Article  PubMed  CAS  Google Scholar 

  • Arnold JC (2005) The role of endocannabinoid transmission in cocaine addiction. Pharmacol Biochem Behav 81:396–406

    Article  PubMed  CAS  Google Scholar 

  • Bernardi RE, Lattal KM, Berger SP (2006) Postretrieval propranolol disrupts a cocaine conditioned place preference. Neuroreport 17:1443–1447

    Article  PubMed  CAS  Google Scholar 

  • Bird CM, Burgess N (2008) The hippocampus and memory: insights from spatial processing. Nat Rev Neurosci 9:182–194

    Article  PubMed  CAS  Google Scholar 

  • Bucherelli C, Baldi E, Mariottini C, Passani MB, Blandina P (2006) Aversive memory reactivation engages in the amygdala only some neurotransmitters involved in consolidation. Learn Mem 13:426–430

    Article  PubMed  CAS  Google Scholar 

  • Campeau S, Davis M (1995) Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli. J Neurosci 15:2301–2311

    PubMed  CAS  Google Scholar 

  • Castane A, Valjent E, Ledent C, Parmentier M, Maldonado R, Valverde O (2002) Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 43:857–867

    Article  PubMed  CAS  Google Scholar 

  • Chiang YC, Chen JC (2007) The role of the cannabinoid type 1 receptor and down-stream cAMP/DARPP-32 signal in the nucleus accumbens of methamphetamine-sensitized rats. J Neurochem 103:2505–2517

    Article  PubMed  CAS  Google Scholar 

  • Clarke JR, Rossato JI, Monteiro S, Bevilaqua LR, Izquierdo I, Cammarota M (2008) Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory. Neurobiol Learn Mem 90:374–381

    Article  PubMed  CAS  Google Scholar 

  • Cohen C, Kodas E, Griebel G (2005) CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav 81:387–395

    Article  PubMed  CAS  Google Scholar 

  • Colombo G, Vacca G, Serra S, Carai MA, Gessa GL (2004) Suppressing effect of the cannabinoid CB1 receptor antagonist, SR 141716, on alcohol’s motivational properties in alcohol-preferring rats. Eur J Pharmacol 498:119–123

    Article  PubMed  CAS  Google Scholar 

  • Darke S, Kaye S, McKetin R, Duflou J (2008) Major physical and psychological harms of methamphetamine use. Drug Alcohol Rev 27:253–262

    Article  PubMed  Google Scholar 

  • de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, Quillfeldt JA (2005) Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats. Neurobiol Learn Mem 83:119–124

    Article  PubMed  CAS  Google Scholar 

  • de Oliveira Alvares L, Genro BP, Vaz Breda R, Pedroso MF, Da Costa JC, Quillfeldt JA (2006) AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats. Brain Res 1075:60–67

    Article  PubMed  CAS  Google Scholar 

  • de Oliveira Alvares L, Genro BP, Diehl F, Quillfeldt JA (2008) Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms. Neurobiol Learn Mem 12:12

    Google Scholar 

  • De Vries TJ, Schoffelmeer AN (2005) Cannabinoid CB1 receptors control conditioned drug seeking. Trends Pharmacol Sci 26:420–426

    Article  PubMed  CAS  Google Scholar 

  • De Vries TJ, Shaham Y, Homberg JR, Crombag H, Schuurman K, Dieben J, Vanderschuren LJ, Schoffelmeer AN (2001) A cannabinoid mechanism in relapse to cocaine seeking. Nat Med 7:1151–1154

    Article  PubMed  CAS  Google Scholar 

  • Degenhardt L, Roxburgh A, Black E, Bruno R, Campbell G, Kinner S, Fetherston J (2008) The epidemiology of methamphetamine use and harm in Australia. Drug Alcohol Rev 27:243–252

    Article  PubMed  Google Scholar 

  • Eichenbaum H, Yonelinas AP, Ranganath C (2007) The medial temporal lobe and recognition memory. Annu Rev Neurosci 30:123–152

    Article  PubMed  CAS  Google Scholar 

  • Fang YX, Wang YB, Shi J, Liu ZM, Lu L (2006) Recent trends in drug abuse in China. Acta Pharmacol Sin 27:140–144

    Article  PubMed  CAS  Google Scholar 

  • Fattore L, Vigano D, Fadda P, Rubino T, Fratta W, Parolaro D (2007) Bidirectional regulation of mu-opioid and CB1-cannabinoid receptor in rats self-administering heroin or WIN 55,212-2. Eur J Neurosci 25:2191–2200

    Article  PubMed  Google Scholar 

  • Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284

    Article  PubMed  CAS  Google Scholar 

  • Gessa GL, Serra S, Vacca G, Carai MA, Colombo G (2005) Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and motivational properties of alcohol in alcohol-preferring sP rats. Alcohol Alcohol 40:46–53

    PubMed  CAS  Google Scholar 

  • Griffiths P, Mravcik V, Lopez D, Klempova D (2008) Quite a lot of smoke but very limited fire—the use of methamphetamine in Europe. Drug Alcohol Rev 27:236–242

    Article  PubMed  Google Scholar 

  • Harris GC, Wimmer M, Aston-Jones G (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437:556–559

    Article  PubMed  CAS  Google Scholar 

  • Hayase T, Yamamoto Y, Yamamoto K (2005) Persistent anxiogenic effects of a single or repeated doses of cocaine and methamphetamine: interactions with endogenous cannabinoid receptor ligands. Behav Pharmacol 16:395–404

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Tristan R, Arevalo C, Canals S, Leret ML (2000) The effects of acute treatment with delta9-THC on exploratory behaviour and memory in the rat. J Physiol Biochem 56:17–24

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Bidaut-Russell M, Devane WA, Melvin LS, Johnson MR, Herkenham M (1990) The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci 13:420–423

    Article  PubMed  CAS  Google Scholar 

  • Hungund BL, Basavarajappa BS (2004) Role of endocannabinoids and cannabinoid CB1 receptors in alcohol-related behaviors. Ann N Y Acad Sci 1025:515–527

    Article  PubMed  CAS  Google Scholar 

  • Hyman SE (2005) Addiction: a disease of learning and memory. Am J Psychiatry 162:1414–1422

    Article  PubMed  Google Scholar 

  • Hyman SE, Malenka RC, Nestler EJ (2006) Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 29:565–598

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW (2007) Cocaine and amphetamine-like psychostimulants: neurocircuitry and glutamate neuroplasticity. Dialogues Clin Neurosci 9:389–397

    PubMed  Google Scholar 

  • Katona I, Rancz EA, Acsady L, Ledent C, Mackie K, Hajos N, Freund TF (2001) Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci 21:9506–9518

    PubMed  CAS  Google Scholar 

  • Kobilo T, Hazvi S, Dudai Y (2007) Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memory. Eur J Neurosci 25:3417–3421

    Article  PubMed  Google Scholar 

  • Kuo YM, Liang KC, Chen HH, Cherng CG, Lee HT, Lin Y, Huang AM, Liao RM, Yu L (2007) Cocaine-but not methamphetamine-associated memory requires de novo protein synthesis. Neurobiol Learn Mem 87:93–100

    Article  PubMed  CAS  Google Scholar 

  • Laurent V, Marchand AR, Westbrook RF (2008) The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear. Learn Mem 15:304–314

    Article  PubMed  CAS  Google Scholar 

  • Le Foll B, Goldberg SR (2005) Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther 312:875–883

    Article  PubMed  CAS  Google Scholar 

  • Li YQ, Li FQ, Wang XY, Wu P, Zhao M, Xu CM, Shaham Y, Lu L (2008a) Central amygdala extracellular signal-regulated kinase signaling pathway is critical to incubation of opiate craving. J Neurosci 28:13248–13257

    Article  PubMed  CAS  Google Scholar 

  • Li F, Fang Q, Liu Y, Zhao M, Li D, Wang J, Lu L (2008b) Cannabinoid CB(1) receptor antagonist rimonabant attenuates reinstatement of ketamine conditioned place preference in rats. Eur J Pharmacol 589:122–126

    Article  PubMed  CAS  Google Scholar 

  • Lin HC, Mao SC, Gean PW (2006) Effects of intra-amygdala infusion of CB1 receptor agonists on the reconsolidation of fear-potentiated startle. Learn Mem 13:316–321

    Article  PubMed  CAS  Google Scholar 

  • Lu L, Koya E, Zhai H, Hope BT, Shaham Y (2006) Role of ERK in cocaine addiction. Trends Neurosci 29:695–703

    Article  PubMed  CAS  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    Article  PubMed  CAS  Google Scholar 

  • Maxwell JC, Rutkowski BA (2008) The prevalence of methamphetamine and amphetamine abuse in North America: a review of the indicators, 1992–2007. Drug Alcohol Rev 27:229–235

    Article  PubMed  Google Scholar 

  • Michels, Fang YX, Zhao D, Zhao LY, Lu L (2007) Comparison of drug abuse in Germany and China. Acta Pharmacol Sin 28:1505–1518

    Article  PubMed  CAS  Google Scholar 

  • Miller CA, Marshall JF (2005) Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Neuron 47:873–884

    Article  PubMed  CAS  Google Scholar 

  • Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

    Article  PubMed  CAS  Google Scholar 

  • Nader K (2003) Memory traces unbound. Trends Neurosci 26:65–72

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ (2001) Molecular neurobiology of addiction. Am J Addict 10:201–217

    Article  PubMed  CAS  Google Scholar 

  • Niyuhire F, Varvel SA, Thorpe AJ, Stokes RJ, Wiley JL, Lichtman AH (2007) The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific. Psychopharmacology (Berl) 191:223–231

    Article  CAS  Google Scholar 

  • Pluddemann A, Myers BJ, Parry CD (2008) Surge in treatment admissions related to methamphetamine use in Cape Town, South Africa: implications for public health. Drug Alcohol Rev 27:185–189

    Article  PubMed  Google Scholar 

  • Pulvirenti L, Koob GF (1994) Dopamine receptor agonists, partial agonists and psychostimulant addiction. Trends Pharmacol Sci 15:374–379

    Article  PubMed  CAS  Google Scholar 

  • Robinson MJ, Franklin KB (2007) Effects of anisomycin on consolidation and reconsolidation of a morphine-conditioned place preference. Behav Brain Res 178:146–153

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47(Suppl 1):33–46

    Article  PubMed  CAS  Google Scholar 

  • Song M, Wang XY, Zhao M, Zhai HF, Lu L (2007) Role of stress in acquisition of alcohol-conditioned place preference in adolescent and adult mice. Alcohol Clin Exp Res 31:2001–2005

    Article  PubMed  Google Scholar 

  • Spiers HJ, Maguire EA, Burgess N (2001) Hippocampal amnesia. Neurocase 7:357–382

    Article  PubMed  CAS  Google Scholar 

  • Takahashi RN, Pamplona FA, Fernandes MS (2005) The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze. Neurosci Lett 380:270–275

    Article  PubMed  CAS  Google Scholar 

  • Treweek J, Wee S, Koob GF, Dickerson TJ, Janda KD (2007) Self-vaccination by methamphetamine glycation products chemically links chronic drug abuse and cardiovascular disease. Proc Natl Acad Sci USA 104:11580–11584

    Article  PubMed  CAS  Google Scholar 

  • Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393–411

    Article  PubMed  CAS  Google Scholar 

  • Valjent E, Corbille AG, Bertran-Gonzalez J, Herve D, Girault JA (2006) Inhibition of ERK pathway or protein synthesis during reexposure to drugs of abuse erases previously learned place preference. Proc Natl Acad Sci USA 103:2932–2937

    Article  PubMed  CAS  Google Scholar 

  • Vezina P (2004) Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27:827–839

    Article  PubMed  CAS  Google Scholar 

  • Vigano D, Valenti M, Cascio MG, Di Marzo V, Parolaro D, Rubino T (2004) Changes in endocannabinoid levels in a rat model of behavioural sensitization to morphine. Eur J Neurosci 20:1849–1857

    Article  PubMed  Google Scholar 

  • Vinklerova J, Novakova J, Sulcova A (2002) Inhibition of methamphetamine self-administration in rats by cannabinoid receptor antagonist AM 251. J Psychopharmacol 16:139–143

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Liu J, Harvey-White J, Zimmer A, Kunos G (2003) Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice. Proc Natl Acad Sci USA 100:1393–1398

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Fang Q, Liu Z, Lu L (2006) Region-specific effects of brain corticotropin-releasing factor receptor type 1 blockade on footshock-stress- or drug-priming-induced reinstatement of morphine conditioned place preference in rats. Psychopharmacology (Berl) 185:19–28

    Article  CAS  Google Scholar 

  • Wang XY, Zhao M, Ghitza UE, Li YQ, Lu L (2008) Stress impairs reconsolidation of drug memory via glucocorticoid receptors in the basolateral amygdala. J Neurosci 28:5602–5610

    Article  PubMed  CAS  Google Scholar 

  • White NM (1996) Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction 91:921–949 discussion 951–965

    Article  PubMed  CAS  Google Scholar 

  • Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296:678–682

    Article  PubMed  CAS  Google Scholar 

  • Wolff MC, Leander JD (2003) SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task. Eur J Pharmacol 477:213–217

    Article  PubMed  CAS  Google Scholar 

  • Xi ZX, Gilbert JG, Peng XQ, Pak AC, Li X, Gardner EL (2006) Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: role of glutamate in the nucleus accumbens. J Neurosci 26:8531–8536

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto T, Takada K (2000) Role of cannabinoid receptor in the brain as it relates to drug reward. Jpn J Pharmacol 84:229–236

    Article  PubMed  CAS  Google Scholar 

  • Zhai HF, Zhang ZY, Zhao M, Qiu Y, Ghitza UE, Lu L (2007) Conditioned drug reward enhances subsequent spatial learning and memory in rats. Psychopharmacology (Berl) 195:193–201

    Article  CAS  Google Scholar 

  • Zhao M, Zhang ZY, Zhai HF, Qiu Y, Lu L (2007) Effects of stress during reactivation on rewarding memory. Neuroreport 18:1153–1156

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by the National Basic Research Program of China (Nos. 2007CB512302 and 2009CB522004), the National High Technology Research and Development Program of China (863 Program, 2006AA02Z4D1), and the Natural Science Foundation of China (Nos. 30670713 and 30725016).

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Authors and Affiliations

  1. Insititute of Mental Health and Hebei Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, Shijiazhuang, 050031, China

    Lu-lu Yu & Xue-yi Wang

  2. National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing, China

    Mei Zhao, Yu Liu, Yan-qin Li, Fang-qiong Li, Xiaoyi Wang, Yan-xue Xue & Lin Lu

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  1. Lu-lu Yu
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  2. Xue-yi Wang
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Correspondence to Xue-yi Wang or Lin Lu.

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Yu, Ll., Wang, Xy., Zhao, M. et al. Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice. Psychopharmacology 204, 203–211 (2009). https://doi.org/10.1007/s00213-008-1450-y

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