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New Approaches to Addiction Treatment Based on Learning and Memory

Part of the Current Topics in Behavioral Neurosciences book series (CTBN,volume 13)

Abstract

Preclinical studies suggest that physiological learning processes are similar to changes observed in addicts at the molecular, neuronal, and structural levels. Based on the importance of classical and instrumental conditioning in the development and maintenance of addictive disorders, many have suggested cue-exposure-based extinction training of conditioned, drug-related responses as a potential new treatment of addiction. It may also be possible to facilitate this extinction training with pharmacological compounds that strengthen memory consolidation during cue exposure. Another potential therapeutic intervention would be based on the so-called reconsolidation theory. According to this hypothesis, already-consolidated memories return to a labile state when reactivated, allowing them to undergo another phase of consolidation–reconsolidation, which can be pharmacologically manipulated. These approaches suggest that the extinction of drug-related memories may represent a viable treatment strategy in the future treatment of addiction.

Keywords

  • Addiction
  • Dependence
  • Reconsolidation
  • LTP
  • Reward
  • Extinction
  • Cue exposure

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Abbreviations

BLA:

Basolateral amygdala

DCS:

D-cycloserine

LTD:

Long time depression

LTP:

Long-term potentiation

NAc:

Nucleus accumbens

NMDA:

N-methyl-D-aspartate

PFC:

Prefrontal cortex

VTA:

Ventral tegmental area

References

  • Alberini CM (2005) Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci 28:51–56

    CAS  PubMed  CrossRef  Google Scholar 

  • Bernardi RE, Lattal KM, Berger SP (2007) Anisomycin disrupts a contextual memory following reactivation in a cocaine-induced locomotor activity paradigm. Behav Neurosci 121(1):156–163

    CAS  PubMed  CrossRef  Google Scholar 

  • Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28:309–369

    CAS  PubMed  CrossRef  Google Scholar 

  • Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356

    CAS  PubMed  Google Scholar 

  • Boening JA (2001) Neurobiology of an addiction memory. J Neural Transm 108:755–765

    CAS  PubMed  CrossRef  Google Scholar 

  • Botreau F, Paolone G, Stewart J (2006) D-cycloserine facilitates extinction of a cocaine-induced conditioned place preference. Behav Brain Res 172:173–178

    CAS  PubMed  CrossRef  Google Scholar 

  • Cai WH, Blundell J, Han J, Greene RW, Powell CM (2006) Postreactivation glucocorticoids impair recall of established fear memory. J Neurosci 26:9560–9566

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Chambless DL, Ollendick TH (2001) Empirically supported psychological interventions. Annu Rev Psychol 52:716

    CrossRef  Google Scholar 

  • Chklovskii DB, Mel BW, Svoboda K (2004) Cortical rewiring and information storage. Nature 431:782–788

    CAS  PubMed  CrossRef  Google Scholar 

  • Conklin CA, Tiffany ST (2002) Applying extinction research and theory to cue-exposure addiction treatments. Addiction 97:155–167

    PubMed  CrossRef  Google Scholar 

  • Cooke SF, Bliss TV (2006) Plasticity in the human central nervous system. Brain 129:1659–1673

    CAS  PubMed  CrossRef  Google Scholar 

  • Dalley JW, Laane K, Theobald DE, Armstrong HC, Corlett PR, Chudasama Y, Robbins TW (2005) Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens. Proc Natl Acad Sci U S A 102:6189–6194

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Davis M, Ressler K, Rothbaum BO, Richardson R (2006) Effects of D-cycloserine on extinction: translation from preclinical to clinical work. Biol Psychiatry 60:369–375

    CAS  PubMed  CrossRef  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Di Ciano P, Everitt BJ (2001) Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior. Neuropsychopharmacology 25:341–360

    CAS  PubMed  CrossRef  Google Scholar 

  • Drummond DC, Glautier S (1994) A controlled trial of cue exposure treatment in alcohol dependence. J Consult Clin Psychol 62:809–817

    CAS  PubMed  CrossRef  Google Scholar 

  • Drummond DC, Cooper T, Glautier SP (1990) Conditioned learning in alcohol dependence: implications for cue exposure treatment. Br J Addict 85:725–743

    CAS  PubMed  CrossRef  Google Scholar 

  • Duvarci S, Nader K (2004) Characterization of fear memory reconsolidation. J Neurosci 24:9269–9275

    CAS  PubMed  CrossRef  Google Scholar 

  • Engblom D, Bilbao-Leis A, Sanchis-Segura C, Dahan L, Perreau-Lenz S, Balland M, Rodriguez Parkitna J, Lujan R, Halbout B, Mameli M, Parlato R, Sprengel R, Lüscher C, Schütz G, Spanagel R (2008) Glutamate receptors on dopamine neurons control the persistence of cocaine-seeking. Neuron 59:497–508

    CAS  PubMed  CrossRef  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489

    CAS  PubMed  CrossRef  Google Scholar 

  • Everitt B, Dickinson A, Robbins TW (2001) The neuropsychological basis of addictive behavior. Brain Res Rev 36:129–138

    CAS  PubMed  CrossRef  Google Scholar 

  • Falls WA, Miserendino MJ, Davis M (1992) Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci 12:854–863

    CAS  PubMed  Google Scholar 

  • Forcato C, Burgos VL, Argibay PF, Molina VA, Pedreira ME, Maldonado H (2007) Reconsolidation of declarative memory in humans. Learn Mem 14:295–303

    PubMed  CrossRef  Google Scholar 

  • Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652

    PubMed Central  PubMed  CrossRef  Google Scholar 

  • Guastella AJ, Lovibonda PF, Daddsa MR, Mitchell P, Richardson R (2007) A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans. Beh ResTher 45:663–672

    Google Scholar 

  • Harris GC, Aston-Jones G (2003) Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment. Neuropsychopharmacology 28:73–76

    CAS  PubMed  CrossRef  Google Scholar 

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

    PubMed  CrossRef  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

    CAS  PubMed  CrossRef  Google Scholar 

  • Ito R, Robbins TW, Everitt BJ (2004) Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci 7:389–397

    CAS  PubMed  CrossRef  Google Scholar 

  • Jay TM (2003) Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog Neurobiol 69:375–390

    CAS  PubMed  CrossRef  Google Scholar 

  • Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162:1403–1413

    PubMed  CrossRef  Google Scholar 

  • Kandel ER, Schwartz JH, Jessel TM (2000) Principles of neural science. McGraw-Hill, New York

    Google Scholar 

  • Karler R, Calder LD, Chaudhry IA, Turkanis SA (1989) Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801. Life Sci 45:599–606

    CAS  PubMed  CrossRef  Google Scholar 

  • Kauer JA (2004) Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu Rev Physiol 66:447–475

    CAS  PubMed  CrossRef  Google Scholar 

  • Kauer JA, Malenka RC (2007) Synaptic plasticity and addiction. Nat Rev Neurosci 8:844–858

    CAS  PubMed  CrossRef  Google Scholar 

  • Kindt M, Soeter M, Vervliet B (2009) Beyond extinction: erasing human fear responses and preventing the return of fear. Nat Neurosci 12(3):256–258

    CAS  PubMed  CrossRef  Google Scholar 

  • Lee JL (2009) Reconsolidation: maintaining memory relevance. Trends Neurosci 32(8):413–420

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Lee JL, Di Ciano P, Thomas KL, Everitt BJ (2005) Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior. Neuron 47:795–801

    CAS  PubMed  CrossRef  Google Scholar 

  • Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46:703–713

    CAS  PubMed  CrossRef  Google Scholar 

  • Loeber S, Mann K (2006) Entwicklung einer evidenzbasierten Psychotherapie bei Alkoholismus: Eine Übersicht. Nervenarzt 77:558–566

    CAS  PubMed  CrossRef  Google Scholar 

  • Lüscher C, Huber KM (2010) Group 1 mGluR-dependent synaptic long-term depression (mGluR-LTD): mechanisms and implications for circuitry and disease. Neuron; 65(4):445–459

    CrossRef  Google Scholar 

  • Malenka RC (2003) The long-term potential of LTP. Nat Rev Neurosci 4:923–926

    CAS  PubMed  CrossRef  Google Scholar 

  • Mameli M, Halbout B, Creton C, Spanagel R, Lüscher C (2009) Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the nucleus accumbens. Nat Neurosci 12:1036–1041

    CAS  PubMed  CrossRef  Google Scholar 

  • Mann K, Schafer DR, Langle G, Ackermann K, Croissant B (2005) The long-term course of alcoholism, 5, 10 and 16 years after treatment. Addiction 100:797–805

    PubMed  CrossRef  Google Scholar 

  • Marissen MA, Franken IH, Blanken P, van den Brink W, Hendriks VM (2007) Cue exposure therapy for the treatment of opiate addiction: results of a randomized controlled clinical trial. Psychother Psychosom 76:97–105

    PubMed  CrossRef  Google Scholar 

  • McBain CJ, Mayer ML (1994) N-methyl-D-aspartic acid receptor structure and function. Physiol Rev 74:723–760

    CAS  PubMed  Google Scholar 

  • McCusker CG (2001) Cognitive biases and addiction: an evolution in theory and method. Addiction 96:47–56

    CAS  PubMed  CrossRef  Google Scholar 

  • McCusker CG, Brown K (1995) Cue-exposure to alcohol-associated stimuli reduces autonomic reactivity, but not craving and anxiety, in dependent drinkers. Alcohol Alcohol 30:319–327

    CAS  PubMed  Google Scholar 

  • McFarland K, Lapish CC, Kalivas PW (2003) Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23:3531–3537

    CAS  PubMed  Google Scholar 

  • Milekic MH, Brown SD, Castellini C, Alberini CM (2006) Persistent disruption of an established morphine conditioned place preference. J Neurosci 26(11):3010–3020

    CAS  PubMed  CrossRef  Google Scholar 

  • Misanin JR, Miller RR, Lewis DJ (1968) Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science 160:554–555

    CAS  PubMed  CrossRef  Google Scholar 

  • Montague PR, Hyman SE, Cohen JD (2004) Computational roles for dopamine in behavioural control. Nature 431:760–767

    CAS  PubMed  CrossRef  Google Scholar 

  • Monti PM, Rohsenow DJ, Rubonis AV, Niaura RS, Sirota AD, Colby SM, Goddard P, Abrams DB (1993) Cue exposure with coping skills treatment for male alcoholics: a preliminary investigation. J Consult Clin Psychol 61:1011–1019

    CAS  PubMed  CrossRef  Google Scholar 

  • Nader K, Wang SH (2006) Fading in. Learn Mem 13:530–535

    PubMed  CrossRef  Google Scholar 

  • Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722–726

    CAS  PubMed  CrossRef  Google Scholar 

  • Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925

    CAS  PubMed  Google Scholar 

  • Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, Hodges L, Davis M (2004) Cognitive enhancers as adjuncts to psychotherapy: Use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 61(11):1136–1144

    PubMed  CrossRef  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    CAS  PubMed  CrossRef  Google Scholar 

  • Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive sensitization view. Addiction 95(2):S91–S117

    PubMed  Google Scholar 

  • Robinson TE, Berridge KC (2001) Incentive-sensitization and addiction. Addiction 96:103–114

    CAS  PubMed  CrossRef  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

    CAS  PubMed  CrossRef  Google Scholar 

  • Rohsenow DJ, Monti PM, Rubonis AV, Gulliver SB, Colby SM, Binkoff JA, Abrams DB (2001) Cue exposure with coping skills training and communication skills training for alcohol dependence: 6- and 12-month outcomes. Addiction 96:1161–1174

    CAS  PubMed  CrossRef  Google Scholar 

  • Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582

    CAS  PubMed  CrossRef  Google Scholar 

  • Santini E, Muller RU, Quirk GJ (2001) Consolidation of extinction learning involves transfer from NMDA-independent to NMDA-dependent memory. J Neurosci 21:9009–9017

    CAS  PubMed  Google Scholar 

  • Scheurich A, Loerch B, Szegedi A, Hautzinger M, Schmidt LG (2004) Cue exposure: differential effects on cue reactivity and drinking outcome measures. Alcohol Clin Exp Res 28:65A

    CrossRef  Google Scholar 

  • Schiller D, Monfils MH, Raio CM, Johnson DC, Ledoux JE, Phelps EA (2010) Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463(7277):49–53

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593–1599

    CAS  PubMed  CrossRef  Google Scholar 

  • Schwabe L, Wolf OT (2010) Stress impairs the reconsolidation of autobiographical memories. Neurobiol Learn Mem 94:153–157

    PubMed  CrossRef  Google Scholar 

  • Sitharthan T, Sitharthan G, Hough MJ, Kavanagh DJ (1997) Cue exposure in moderation drinking: a comparison with cognitive-behavior therapy. J Consult Clin Psychol 65:878–882

    CAS  PubMed  CrossRef  Google Scholar 

  • Soeter M, Kindt M (2010) Dissociating response systems: erasing fear from memory. Neurobiol Learn Mem 94(1):30–41

    PubMed  CrossRef  Google Scholar 

  • Tollenaar MS, Elzinga BM, Spinhoven P, Everaerd W (2009) Immediate and prolonged effects of cortisol, but not propranolol, on memory retrieval in healthy young men. Neurobiol Learn Mem 91:23–31

    CAS  PubMed  CrossRef  Google Scholar 

  • Tronson NC, Taylor JR (2007) Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8(4):262–275

    CAS  PubMed  CrossRef  Google Scholar 

  • Ungless MA, Whistler JL, Malenka RC, Bonci A (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411:583–587

    CAS  PubMed  CrossRef  Google Scholar 

  • Valjent E, Corbille AG, Bertran-Gonzalez J, Hervé 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 U S A 103:2932–2937

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • von der Goltz C, Kiefer F (2009) Learning and memory in the aetiopathogenesis of addiction: future implications for therapy? Eur Arch Psychiatry Clin Neurosci 259(2):S183–S187

    CrossRef  Google Scholar 

  • von der Goltz C, Vengeliene V, Bilbao A, Perreau-Lenz S, Pawlak CR, Kiefer F, Spanagel R (2009) Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories. Psychopharmacology 205(3):389–397

    CrossRef  Google Scholar 

  • Walker MP, Brakefield T, Hobson JA, Stickgold R (2003) Dissociable stages of human memory consolidation and reconsolidation. Nature 425(6958):616–620

    CAS  PubMed  CrossRef  Google Scholar 

  • Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263

    CAS  PubMed  CrossRef  Google Scholar 

  • Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494

    CAS  PubMed  CrossRef  Google Scholar 

  • Zhao LY, Zhang XL, Shi J, Epstein DH, Lu L (2008) Psychosocial stress after reactivation of drug-related memory impairs later recall in abstinent heroin addicts. Psychopharmacology 203(3):599–608

    PubMed Central  PubMed  CrossRef  Google Scholar 

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Acknowledgments

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) (grant SFB 636, D6), as well as the Bundesministerium für Bildung und Forschung (grant NGFN 01 GS08152, SP 13).

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Correspondence to Falk Kiefer .

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Kiefer, F., Dinter, C. (2011). New Approaches to Addiction Treatment Based on Learning and Memory. In: Sommer, W., Spanagel, R. (eds) Behavioral Neurobiology of Alcohol Addiction. Current Topics in Behavioral Neurosciences, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28720-6_147

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