Skip to main content
SpringerLink
Log in

Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats

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

An Erratum to this article was published on 07 December 2013

Abstract

Rationale

Drug addicts constantly relapse to drug seeking after recall of memories linked to the drug experience. It is believed that a successful application of therapies that block memory reconsolidation may end the continuous cycle of drug relapse.

Objectives

The purpose of this study is to investigate whether modulation of the endocannabinoid system would impact the reconsolidation of opioid-related hedonic memories in rats previously paired to morphine context.

Methods

Male Wistar rats were trained to acquire a morphine-conditioned place preference (CPP). One week later, morphine-CPP memory was reactivated by a brief exposure to a drug-paired context. Immediately after the memory reactivation session, independent groups of morphine-trained rats received a single subcutaneous injection of different doses of cannabinoid CB1 receptor antagonist rimonabant, CB2-selective antagonist AM630, potent CB1/CB2 agonist WIN 55,212-2, inhibitor of enzyme fatty acid amide hydrolase URB597, or vehicle. Morphine-CPP was retested 1 and 2 weeks after reactivation.

Results

Blockade of CB1 (but not CB2) cannabinoid receptors impaired CPP reconsolidation of morphine-CPP at both tests 1 and 2 weeks post-reactivation, whereas direct activation of cannabinoid receptors did not produce significant effects on morphine-induced CPP. However, boosting endocannabinoid signaling by inhibition of anandamide metabolism promoted a transient CB1-dependent enhancement of the CPP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  • Blednov YA, Cravatt BF, Boehm SL, Walker D, Harris RA (2007) Role of endocannabinoids in alcohol consumption and intoxication: studies of mice lacking fatty acid amide hydrolase. Neuropsychopharmacology 32:1570–1582

    Article  CAS  PubMed  Google Scholar 

  • Braida D, Pozzi M, Parolaro D, Sala M (2001) Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system. Eur J Pharmacol 413:227–234

    Article  CAS  PubMed  Google Scholar 

  • Brown TE, Lee BR, Sorg BA (2008) The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats. Learn Mem 15(12):857–865

    Article  PubMed Central  PubMed  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  CAS  PubMed  Google Scholar 

  • Chaperon F, Soubrie P, Puech AJ, Thiebot MH (1998) Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats. Psychopharmacology 135:324–332

    Article  CAS  PubMed  Google Scholar 

  • de Oliveira Alvares L, Pasqualini Genro B, Diehl F, Molina VA, Quillfeldt JA (2008) Oposite action of hippocampal CB1 receptors in memory reconsolidation and extinction. Neuroscience 154(4):1648–1655

    Article  PubMed  Google Scholar 

  • De Vries TJ, Schoffelmeer ANM (2005) Cannabinoid CB1 receptors control conditioned drug seeking. Trends Pharmacol Sci 26(8):420–426

    Article  PubMed  Google Scholar 

  • Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacol (Berl) 189:1–16

    Article  CAS  Google Scholar 

  • Fang Q, Li FQ, Li YQ, Xue YX, He YY, Liu JF, Lu L, Wang JS (2011) Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward associated memory in rats. Pharmacol Biochem Behav 99:738–742

    Article  CAS  PubMed  Google Scholar 

  • Fattore L, Deiana S, Spano SM, Cossu G, Fadda P, Scherma M, Fratta W (2005) Endocannabinoid system and opioid addiction: behavioural aspects. Pharmacol Biochem Behav 81(2):343–359

    Article  CAS  PubMed  Google Scholar 

  • Fegley D, Gaetani S, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide oleoylethanolamide deactivation. J Pharmacol Exp Ther 313:352–358

    Article  CAS  PubMed  Google Scholar 

  • Gamaleddin I, Zvonok A, Makriyannis A, Goldberg SR, Le Foll B (2012) Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking. PLoS One 7(1):e 29900

    Article  CAS  Google Scholar 

  • Gobbi G, Bambico FR, Manqieri R, Bortalato M, Campolongo P, Solinas M, Cassano T et al (2005) Antidepressant like activity and modulation of brain monominergic transmission by blockade of anandaminde hydrolysis. Proc Natl Acad Sci U S A 102:18620–18625

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Harloe JP, Thorpe AJ, Lichtman AH (2008) Differential endocannabinoid regulation of extinction in appetitive and aversive Barnes maze tasks. Learn Mem 15:806–809

    Article  PubMed Central  PubMed  Google Scholar 

  • Ishiguro H, Iwasaki S, Teasenfitz L, Higuchi S, Horiuchi Y, Saito T, Arinami T et al (2007) Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans. Pharmacogenomics J 7:380–385

    Article  CAS  PubMed  Google Scholar 

  • Justinova Z, Mangieri RA, Bortolato M, Chefer SI, Mukhin AG, Clapper JR, King AR et al (2008) Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry 64:930–937

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, Mor M et al (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9:76–81

    Article  CAS  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

    CAS  PubMed  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 

  • 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  CAS  PubMed Central  PubMed  Google Scholar 

  • Lutz B (2007) The endocannabinoid system and extinction learning. Mol Neurobiol 36:92–101

    Article  CAS  PubMed  Google Scholar 

  • Maldonado R, Valverde O, Berrendero F (2006) Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 29(4):225–232

    Article  CAS  PubMed  Google Scholar 

  • Manwell LA, Satvat E, Lang ST, Allen CP, Leri F, Parker LA (2009) FAAH inhibitor, URB-597, promotes extinction and CB1 antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats. Pharmacol Biochem Behav 94:154–162

    Article  CAS  PubMed  Google Scholar 

  • Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H et al (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534

    Article  CAS  PubMed  Google Scholar 

  • Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O (2000) Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice. Eur J Neurosci 12:4038–4046

    Article  CAS  PubMed  Google Scholar 

  • Mazzola C, Medalie J, Scherma M, Panlilio LV, Solinas M, Tanda G, Drago F et al (2009) Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors. Learn Mem 16:332–337

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Milekic MH, Brown SD, Castellini C, Alberini CM (2006) Persistent disruption of an established morphine conditioned place preference. J Neurosci 26:3010–3020

    Article  CAS  PubMed  Google Scholar 

  • Milton AL, Everitt BJ (2010) The psychological and neurochemical mechanisms of drug memory reconsolidation: implications for the treatment of addiction. Eur J Neurosci 31:2308–2319

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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. Psychopharmacol (Berl) 191:223–231

    Article  CAS  Google Scholar 

  • O'Brien CP, Childress AR, McLellan AT, Ehrman R (1992) Classical conditioning in drug-dependent humans. Ann N Y Acad Sci 654:400–415

    Article  PubMed  Google Scholar 

  • O'Sullivan SE (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 152:576–582

    Article  PubMed Central  PubMed  Google Scholar 

  • Pamplona FA, Prediger RD, Pandolfo P, Takahashi RN (2006) The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacol (Berl) 188:641–649

    Article  CAS  Google Scholar 

  • Pamplona FA, Bitencourt RM, Takahashi RN (2008) Short- and long-term effects of cannabinoids on the extinction of contextual fear memory in rats. Neurobiol Learn Mem 90(1):290–293

    Article  CAS  PubMed  Google Scholar 

  • Pandolfo P, Vendruscolo LF, Sordi R, Takahashi RN (2009) Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder. Psychopharmacol (Berl) 205(2):319–326

    Article  CAS  Google Scholar 

  • Pickel VM, Chan J, Kash TL, Rodriguez JJ, MacKie K (2004) Compartment-specific localization of cannabinoid 1 (CB1) and micro-opioid receptors in rat nucleus accumbens. Neuroscience 27:101–112

    Article  Google Scholar 

  • Robbins TW, Ersche KD, Everitt BJ (2008) Drug addiction and the memory systems of the brain. Ann N Y Acad Sci 1141:1–21

    Article  CAS  PubMed  Google Scholar 

  • Scherma M, Panlilio LV, Fadda P, Fattore L, Gamaleddin I, Le Foll B, Justinová Z et al (2008) Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3′-carbamoyl-3-ylester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J Pharmacol Exp Ther 327:482–490

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Singh ME, Verty AN, McGregor IS, Mallet PE (2004) A cannabinoid receptor antagonist attenuates conditioned place preference but not behavioural sensitization to morphine. Brain Res 1026(2):244–253

    Article  CAS  PubMed  Google Scholar 

  • Solinas M, Panlilio LV, Tanda G, Makriyannis A, Matthews SA, Goldberg SR (2005) Cannabinoid agonists but not inhibitors of endogenous cannabinoid transport or metabolism enhance the reinforcing efficacy of heroin in rats. Neuropsychopharmacology 30:2046–2057

    Google Scholar 

  • Starowicz K, Nigam S, Di Marzo V (2007) Biochemistry and pharmacology of endovanilloids. Pharmacol Ther 114(1):13–33

    Article  CAS  PubMed  Google Scholar 

  • Suzuki A, Josselyn SA, Frankland PW, Masushige S, Silva AJ, Kida S (2004) Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24(20):4787–4795

    Article  CAS  PubMed  Google Scholar 

  • Suzuki A, Mukawa T, Tsukagoshi A, Frankland PW, Kida S (2008) Activation of LVGCCs and CB1 receptors required for destabilization of reactivated contextual fear memories. Learn Mem 15:426–433

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Torregrossa MM, Taylor JR (2013) Learning to forget: manipulating extinction and reconsolidation processes to treat addiction. Psychopharmacol (Berl) 226(4):659–672

    Article  CAS  Google Scholar 

  • Trigo JM, Martin-García E, Berrendero F, Robledo P, Maldonado R (2010) The endogenous opioid system: a common substrate in drug addiction. Drug Alcohol Depend 108(3):183–194

    Article  CAS  PubMed  Google Scholar 

  • Varvel SA, Anum EA, Lichtman AH (2005) Disruption of CB (1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacol (Berl) 179:863–872

    Article  CAS  Google Scholar 

  • Wang X, Cen X, Lu L (2001) Noradrenaline in the bed nucleus of the stria terminalis is critical for stress-induced reactivation of morphine-conditioned place preference in rats. Eur J Pharmacol 432:153–161

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ et al (2011) Brain cannabinoid CB2 receptors modulate cocaine's actions in mice. Nat Neurosci 14:1160–1166

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yu LL, Wang XY, Zhao M, Liu Y, Li YQ, Wang X, Xue YX, Lu L (2009) Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reard memory in mice. Psychopharmacol (Berl) 204(2):203–211

    Google Scholar 

Download references

Acknowledgments

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), and Programa de Apoio aos Núcleos de Excelência (PRONEX), all of Brazil. RNT is the holder of a CNPq research fellowship. CR de Carvalho and JS Cruz are supported by scholarships from CNPq.

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory of Psychopharmacology, Department of Pharmacology, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900, Florianopolis, SC, Brazil

    Cristiane Ribeiro De Carvalho, Jéssica Silveira Cruz & Reinaldo Naoto Takahashi

  2. D’Or Institute for Research and Education, Rio de Janeiro, Brazil

    Fabrício Alano Pamplona

Authors
  1. Cristiane Ribeiro De Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabrício Alano Pamplona
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jéssica Silveira Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reinaldo Naoto Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cristiane Ribeiro De Carvalho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Carvalho, C.R., Pamplona, F.A., Cruz, J.S. et al. Endocannabinoids underlie reconsolidation of hedonic memories in Wistar rats. Psychopharmacology 231, 1417–1425 (2014). https://doi.org/10.1007/s00213-013-3331-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3331-2

Keywords

Search

Navigation