, Volume 229, Issue 3, pp 487–491

Deep brain stimulation for the treatment of addiction: basic and clinical studies and potential mechanisms of action




Deep brain stimulation (DBS) has achieved substantial success as a treatment for movement disorders such as Parkinson’s disease. The therapeutic efficacy and relative lack of serious side effects resulted in the expansion of DBS into the treatment of many other diseases, including obsessive–compulsive disorder, Tourette’s, and depression, among others. More recently, a limited number of basic and clinical studies indicated that DBS may also be useful in the treatment of various addictions.


Here, we briefly summarize the history of DBS and review the basic and clinical studies focused on DBS and addiction. We also examine the potential mechanisms that may underlie the effects of DBS.

Results and conclusions

The available data indicate that DBS is a promising therapeutic modality for the treatment of addiction. Thus far, the nucleus accumbens and subthalamic nucleus are the most promising sites for DBS, reversing aspects of addiction. The mechanisms underlying DBS are complex and likely vary from region to region. Emerging evidence indicates that DBS of the nucleus accumbens produces its effects, at least in part, by antidromic activation of cortico-accumbal afferents that stimulate inhibitory medial prefrontal cortex interneurons via recurrent collaterals.


Accumbens Subthalamic nucleus Cocaine DBS 


  1. Baunez C, Dias C, Cador M, Amalric M (2005) The subthalamic nucleus exerts opposite control on cocaine and 'natural' rewards. Nat Neurosci 8:484–489PubMedGoogle Scholar
  2. Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50:344–346PubMedGoogle Scholar
  3. Benabid AL, Koudsie A, Benazzouz A, Piallat B, Krack P, Limousin-Dowsey P, Lebas JF, Pollak P (2001) Deep brain stimulation for Parkinson's disease. Adv Neurol 86:405–412PubMedGoogle Scholar
  4. Benazzouz A, Hallett M (2000) Mechanism of action of deep brain stimulation. Neurology 55:S13–S16PubMedGoogle Scholar
  5. Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental Parkinsonism by lesions of the subthalamic nucleus. Science 249:1436–1438PubMedCrossRefGoogle Scholar
  6. Boraud T, Bezard E, Bioulac B, Gross C (1996) High frequency stimulation of the internal Globus Pallidus (GPi) simultaneously improves Parkinsonian symptoms and reduces the firing frequency of GPi neurons in the MPTP-treated monkey. Neurosci Lett 215:17–20PubMedCrossRefGoogle Scholar
  7. Carter A, Hall W (2011) Proposals to trial deep brain stimulation to treat addiction are premature. Addiction 106:235–237PubMedCrossRefGoogle Scholar
  8. Cornish JL, Duffy P, Kalivas PW (1999) A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93:1359–1367PubMedCrossRefGoogle Scholar
  9. Croft PG (1952) The effect of electrical stimulation of the brain on the perception of pain. J Ment Sci 98:421–426PubMedGoogle Scholar
  10. Delgado JM, Hamlin H, Chapman WP (1952) Technique of intracranial electrode implacement for recording and stimulation and its possible therapeutic value in psychotic patients. Confin Neurol 12:315–319PubMedCrossRefGoogle Scholar
  11. El-Hai J (2005) The lobotomist: a maverick medical genius and his tragic quest to rid the world of mental illness. Wiley, HobokenGoogle Scholar
  12. Eusebio A, Witjas T, Cohen J, Fluchere F, Jouve E, Regis J, Azulay JP (2013) Subthalamic nucleus stimulation and compulsive use of dopaminergic medication in Parkinson's disease. J Neurol Neurosurg Psychiatry 84(8):868–874PubMedCrossRefGoogle Scholar
  13. Ewing SG, Grace AA (2013) Long-term high frequency deep brain stimulation of the nucleus accumbens drives time-dependent changes in functional connectivity in the rodent limbic system. Brain Stimul 6:274–285PubMedCrossRefGoogle Scholar
  14. Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (2009) Optical deconstruction of Parkinsonian neural circuitry. Science 324:354–359PubMedCrossRefGoogle Scholar
  15. Grubert C, Hurlemann R, Bewernick BH, Kayser S, Hadrysiewicz B, Axmacher N, Sturm V, Schlaepfer TE (2011) Neuropsychological safety of nucleus accumbens deep brain stimulation for major depression: effects of 12-month stimulation. World J Biol Psychiatry 12:516–527PubMedCrossRefGoogle Scholar
  16. Hamani C, Richter E, Schwalb JM, Lozano AM (2008) Bilateral subthalamic nucleus stimulation for Parkinson's disease: a systematic review of the clinical literature. Neurosurgery 62(Suppl 2):863–874PubMedGoogle Scholar
  17. Hariz M (2012) Twenty-five years of deep brain stimulation: celebrations and apprehensions. Mov Disord 27:930–933PubMedCrossRefGoogle Scholar
  18. Heimer L, Alheid GF, de Olmos JS, Groenewegen HJ, Haber SN, Harlan RE, Zahm DS (1997) The accumbens: beyond the core-shell dichotomy. J Neuropsychiatry Clin Neurosci 9:354–381PubMedGoogle Scholar
  19. Henderson MB, Green AI, Bradford PS, Chau DT, Roberts DW, Leiter JC (2010) Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats. Neurosurg Focus 29:E12PubMedCrossRefGoogle Scholar
  20. Kalivas PW, Volkow N, Seamans J (2005) Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron 45:647–650PubMedCrossRefGoogle Scholar
  21. Kiss ZH, Mooney DM, Renaud L, Hu B (2002) Neuronal response to local electrical stimulation in rat thalamus: physiological implications for mechanisms of deep brain stimulation. Neuroscience 113:137–143PubMedCrossRefGoogle Scholar
  22. Knapp CM, Tozier L, Pak A, Ciraulo DA, Kornetsky C (2009) Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats. Pharmacol Biochem Behav 92:474–479PubMedCrossRefGoogle Scholar
  23. Knobel D, Aybek S, Pollo C, Vingerhoets FJ, Berney A (2008) Rapid resolution of dopamine dysregulation syndrome (DDS) after subthalamic DBS for Parkinson disease (PD): a case report. Cogn Behav Neurol 21:187–189PubMedCrossRefGoogle Scholar
  24. Kuhn J, Lenartz D, Huff W, Lee S, Koulousakis A, Klosterkoetter J, Sturm V (2007) Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications? J Neurol Neurosurg Psychiatry 78:1152–1153PubMedCrossRefGoogle Scholar
  25. Kuhn J, Lenartz D, Huff W, Lee SH, Koulousakis A, Klosterkoetter J, Sturm V (2009) Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications? BMJ Case Rep 2009Google Scholar
  26. Laitinen LV, Bergenheim AT, Hariz MI (1992) Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease. J Neurosurg 76:53–61PubMedCrossRefGoogle Scholar
  27. Lawrence AD, Evans AH, Lees AJ (2003) Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? Lancet Neurol 2:595–604PubMedCrossRefGoogle Scholar
  28. Lhommee E, Klinger H, Thobois S, Schmitt E, Ardouin C, Bichon A, Kistner A, Fraix V, Xie J, Aya Kombo M, Chabardes S, Seigneuret E, Benabid AL, Mertens P, Polo G, Carnicella S, Quesada JL, Bosson JL, Broussolle E, Pollak P, Krack P (2012) Subthalamic stimulation in Parkinson's disease: restoring the balance of motivated behaviours. Brain 135:1463–1477PubMedCrossRefGoogle Scholar
  29. Lim SY, O'Sullivan SS, Kotschet K, Gallagher DA, Lacey C, Lawrence AD, Lees AJ, O'Sullivan DJ, Peppard RF, Rodrigues JP, Schrag A, Silberstein P, Tisch S, Evans AH (2009) Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson's disease. J Clin Neurosci 16:1148–1152PubMedCrossRefGoogle Scholar
  30. Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, Perret JE, Benabid AL (1995) Effect of Parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345:91–95PubMedCrossRefGoogle Scholar
  31. Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL (1998) Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:1105–1111PubMedCrossRefGoogle Scholar
  32. Liu HY, Jin J, Tang JS, Sun WX, Jia H, Yang XP, Cui JM, Wang CG (2008) Chronic deep brain stimulation in the rat nucleus accumbens and its effect on morphine reinforcement. Addict Biol 13:40–46PubMedCrossRefGoogle Scholar
  33. Lozano AM, Lipsman N (2013) Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron 77:406–424PubMedCrossRefGoogle Scholar
  34. Luigjes J, van den Brink W, Feenstra M, van den Munckhof P, Schuurman PR, Schippers R, Mazaheri A, De Vries TJ, Denys D (2012) Deep brain stimulation in addiction: a review of potential brain targets. Mol Psychiatry 17:572–583PubMedCrossRefGoogle Scholar
  35. Mantione M, van de Brink W, Schuurman PR, Denys D (2010) Smoking cessation and weight loss after chronic deep brain stimulation of the nucleus accumbens: therapeutic and research implications: case report. Neurosurgery 66:E218, discussion E218PubMedCrossRefGoogle Scholar
  36. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660PubMedCrossRefGoogle Scholar
  37. Mazars GJ (1975) Intermittent stimulation of nucleus ventralis posterolateralis for intractable pain. Surg Neurol 4:93–95PubMedGoogle Scholar
  38. McCracken CB, Grace AA (2007) High-frequency deep brain stimulation of the nucleus accumbens region suppresses neuronal activity and selectively modulates afferent drive in rat orbitofrontal cortex in vivo. J Neurosci 27:12601–12610PubMedCrossRefGoogle Scholar
  39. McCracken CB, Grace AA (2009) Nucleus accumbens deep brain stimulation produces region-specific alterations in local field potential oscillations and evoked responses in vivo. J Neurosci 29:5354–5363PubMedCrossRefGoogle Scholar
  40. McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL (2004) Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol 115:1239–1248PubMedCrossRefGoogle Scholar
  41. Montgomery EB Jr, Gale JT (2008) Mechanisms of action of deep brain stimulation (DBS). Neurosci Biobehav Rev 32:388–407PubMedCrossRefGoogle Scholar
  42. Muller UJ, Voges J, Steiner J, Galazky I, Heinze HJ, Moller M, Pisapia J, Halpern C, Caplan A, Bogerts B, Kuhn J (2013) Deep brain stimulation of the nucleus accumbens for the treatment of addiction. Ann N Y Acad Sci 1282:119–128PubMedCrossRefGoogle Scholar
  43. Nowak LG, Bullier J (1998) Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments. Exp Brain Res 118:489–500PubMedCrossRefGoogle Scholar
  44. Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B (1999) Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet 354:1526PubMedCrossRefGoogle Scholar
  45. Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30:215–238PubMedCrossRefGoogle Scholar
  46. Ping A, Xi J, Prasad BM, Wang MH, Kruzich PJ (2008) Contributions of nucleus accumbens core and shell GluR1 containing AMPA receptors in AMPA- and cocaine-primed reinstatement of cocaine-seeking behavior. Brain Res 1215:173–182PubMedCrossRefGoogle Scholar
  47. Rouaud T, Lardeux S, Panayotis N, Paleressompoulle D, Cador M, Baunez C (2010) Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation. Proc Natl Acad Sci USA 107:1196–1200PubMedCrossRefGoogle Scholar
  48. Schmidt HD, Pierce RC (2010) Cocaine-induced neuroadaptations in glutamate transmission: potential therapeutic targets for craving and addiction. Ann N Y Acad Sci 1187:35–75PubMedCrossRefGoogle Scholar
  49. Svennilson E, Torvik A, Lowe R, Leksell L (1960) Treatment of Parkinsonism by stereotatic thermolesions in the pallidal region. A clinical evaluation of 81 cases. Acta Psychiatr Scand 35:358–377PubMedCrossRefGoogle Scholar
  50. Uslaner JM, Crombag HS, Ferguson SM, Robinson TE (2003) Cocaine-induced psychomotor activity is associated with its ability to induce c-fos mRNA expression in the subthalamic nucleus: effects of dose and repeated treatment. Eur J Neurosci 17:2180–2186PubMedCrossRefGoogle Scholar
  51. Valencia-Alfonso CE, Luigjes J, Smolders R, Cohen MX, Levar N, Mazaheri A, van den Munckhof P, Schuurman PR, van den Brink W, Denys D (2012) Effective deep brain stimulation in heroin addiction: a case report with complementary intracranial electroencephalogram. Biol Psychiatry 71:e35–e37PubMedCrossRefGoogle Scholar
  52. Valenstein ES (1986) Great and desperate cures: the rise and decline of psychosurgery and other radical treatments for mental illness. Basic Books, New YorkGoogle Scholar
  53. Vandewalle V, van der Linden C, Groenewegen HJ, Caemaert J (1999) Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus. Lancet 353:724PubMedCrossRefGoogle Scholar
  54. Vassoler FM, Schmidt HD, Gerard ME, Famous KR, Ciraulo DA, Kornetsky C, Knapp CM, Pierce RC (2008) Deep brain stimulation of the nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug seeking in rats. J Neurosci 28:8735–8739PubMedCrossRefGoogle Scholar
  55. Vassoler FM, White SL, Hopkins TJ, Guercio CA, Espallergues J, Berton O, Schmidt HD, Pierce RC (2013) Deep brain stimulation of the nucleus accumbe shell attenuates cocaine reinstatement through local and antidromic activation. J Neurosci (in press)Google Scholar
  56. Vitek JL (2002) Mechanisms of deep brain stimulation: excitation or inhibition. Mov Disord 17(Suppl 3):S69–S72PubMedCrossRefGoogle Scholar
  57. Voges J, Waerzeggers Y, Maarouf M, Lehrke R, Koulousakis A, Lenartz D, Sturm V (2006) Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery–experiences from a single centre. J Neurol Neurosurg Psychiatry 77:868–872PubMedCrossRefGoogle Scholar
  58. Windels F, Bruet N, Poupard A, Urbain N, Chouvet G, Feuerstein C, Savasta M (2000) Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Eur J Neurosci 12:4141–4146PubMedCrossRefGoogle Scholar
  59. Witjas T, Baunez C, Henry JM, Delfini M, Regis J, Cherif AA, Peragut JC, Azulay JP (2005) Addiction in Parkinson's disease: impact of subthalamic nucleus deep brain stimulation. Mov Disord 20:1052–1055PubMedCrossRefGoogle Scholar
  60. Zahm DS (2000) An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev 24:85–105PubMedCrossRefGoogle Scholar
  61. Zhou H, Xu J, Jiang J (2011) Deep brain stimulation of nucleus accumbens on heroin-seeking behaviors: a case report. Biol Psychiatry 69:e41–e42PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Biomedical Sciences, Cummings School of Veterinary MedicineTufts UniversityGraftonUSA

Personalised recommendations