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Future directions in substance dependence research

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Neuropsychopharmacology

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 64))

Abstract

Substance dependence is a major health problem but increasing understanding of its neurobiology is likely to lead to improved prevention and treatment. Fundamental aspects of dependence include tolerance and withdrawal and the fact that the drug becomes the centre of the addict’s world. Neuroimaging has been key in defining underlying neurobiological mechanisms. The activity in particular brain regions has been shown to be altered in addiction. These include the anterior cingulate which is involved in emotional salience and the orbitofrontal cortex, involved in impulse control. Dopamine is the key neurotransmitter since most abused drugs increase its levels, and many pharmacotherapies have targeted this system. The opiate system is also key in mediating the pleasurable effects of some drugs such as alcohol by increasing dopamine levels. The GABA and glutamate systems mediate many of the other effects of alcohol. As the neurobiology of different components of addiction become evident, pharmacological approaches involve exploiting our new understanding which will likely lead to improved treatments.

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References

  • Azari NP, Pie trini P, Horwitz B, Pettigrew KD, Leonard HL, Rapoport JL, Schapiro MB, Swedo SE (1993) Individual differences in cerebral metabolic patterns during pharmacotherapy in obsessive-compulsive disorder: a multiple regression/discriminant analysis of positron emission tomographic data. Biol Psychiatry 34(11): 798–809

    Article  CAS  PubMed  Google Scholar 

  • Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE (1987) Local cerebral glucose metabolic rates in obsessive compulsive disorder: a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry 44(3): 211¡ª 218

    Article  Google Scholar 

  • Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, Alazraki A, Selin CE, Ferng HK, Munford P et al (1992) Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 49(9): 681–689

    Article  CAS  PubMed  Google Scholar 

  • Bergstrom M, Fasth KJ, Kilpatrick G, Ward P, Cable KM, Wipperman MD, Sutherland DR, Langstrom B (2000) Brain uptake and receptor binding of two [HC]labelled selective high affinity NKl-antagonists, GR203040 and GR205171-PET studies in rhesus monkey. Neuropharmacology 39: 664–670

    Article  CAS  PubMed  Google Scholar 

  • Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr (1998) FDG-PET predictors of response to behavioral therapy versus pharmacotherapy in obsessive-compulsive disorder. Psychiatry Res: Neuroimaging 84(1): 1–6

    Article  CAS  PubMed  Google Scholar 

  • Cappendijk SL, Hurd YL, Nylander I, van Ree JM, Terenius L (1999) A heroin-, but not a cocaine-expecting, self-administration state preferentially alters endogenous brain peptides. Eur J Pharmacol 365(2–3): 175–182

    Article  CAS  PubMed  Google Scholar 

  • Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP (1999) Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156(1): 11–8

    CAS  PubMed Central  PubMed  Google Scholar 

  • Daglish MRC, Weinstein A, Malizia AL, Wilson SJ, Melichar JK, Britten S, Brewer C, Lingford-Hughes A, Myles JS, Grasby P, Nutt DJ (2001a) Regional cerebral blood flow changes elicited by craving memories in abstinent opiate-dependent individuals. Am J Psychiatry 158: 1680–1686

    Article  CAS  Google Scholar 

  • Dahchour A, De Witte P (2000) Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol 60: 343–362

    Article  CAS  PubMed  Google Scholar 

  • Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci 93(21): 12040–12045

    Article  CAS  PubMed  Google Scholar 

  • Herz A (1997). Endogenous opioid systems and alcohol addiction. Psychopharmacology 129: 99–111

    Article  CAS  PubMed  Google Scholar 

  • Huston JP, Hasenohrl RU, Boix F, Gerhardt P, Schwarting RK (1993) Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity. Psychopharmacology 112(2–3): 147–62 (Review)

    Article  CAS  PubMed  Google Scholar 

  • Jones AK, Friston KJ, Qi LY, Harris M, Cunningham VJ, Jones T, Feinman C, Frackowiak RS (1991) Sites of action of morphine in the brain. Lancet 338: 825

    Article  CAS  PubMed  Google Scholar 

  • Jorenby DE, Leischow SJ, Nides MA, et al (1999) A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340: 685–691

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward,and allostasis. Neuropsychopharmacology 24: 97–129

    Article  CAS  PubMed  Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Rupniak NM, et al (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281(5383): 1640–1645

    Article  CAS  PubMed  Google Scholar 

  • Law FD, Bailey JE, Allen DS, Melichar JK, Myles JS, Mitcheson MC, Lewis JW, Nutt DJ (1997) The feasibility of abrupt methadone-buprenorphine transfer in British opiate addicts in an out patient setting. Addic Biol 2(2): 191–200

    Article  Google Scholar 

  • Lister RG, Nutt DJ (1987) Is Ro 15–4513 a specific alcohol antagonist? Trends Neurosci 101: 223–225

    Article  Google Scholar 

  • London ED, Ernst M, Grant S, Bonson K, Weinstein A (2000) Orbitofrontal cortex and human drug abuse: functional imaging. Cerebral Cortex 10(3): 334–342

    Article  CAS  PubMed  Google Scholar 

  • Maas LC, Lukas SE, Kaufman MJ, Weiss RD, Daniels SL, Rogers VW, Kukes, TJ, Renshaw PF (1998) Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving. Am J Psychiatry 155: 124–126

    CAS  PubMed  Google Scholar 

  • Malizia AL (2002) The neuroinaging of anxiety. In: Nutt DJ, Ballenger J (eds) Anxiety disorders. Blackwells, pp 201–228

    Google Scholar 

  • Murtra P, Sheasby AM, Hunt SP, De Felipe C (2000) Rewarding effects of opiates are absent in mice lacking the receptor for substance P. Nature 405(6783): 180–183

    Article  CAS  PubMed  Google Scholar 

  • Nutt DJ (1997) Receptor pharmacology of buprenorphine. Buprenorphine ¡ª a substitution agent for the treatment of opioid addiction: a UK perspective. Res Clin Forums 19(2): 9–15

    Google Scholar 

  • Nutt DJ (1999) Alcohol and the brain: pharmacological insights for psychiatrists. Br J Psychiatry 175: 114–119

    Article  CAS  PubMed  Google Scholar 

  • Nutt DJ, Malizia AL (2001) New insights into the role of the GAB A-A benzodiazepine receptor. Br J Psychiatry 179: 390–396

    Article  CAS  PubMed  Google Scholar 

  • Pratt JA, Laurie DJ, McCulloch J (1988) The effects of FG 7142 upon local cerebral glucose utilization suggest overlap between limbic structures important in anxiety and convulsions. Brain Res 475(2): 218–231

    Article  CAS  PubMed  Google Scholar 

  • Pilla M, Perachon S, Sautel F, Garrido F, Mann A, Wermuth CG, Schwartz JC, Everitt BJ, Sokoloff P (1999) Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature 400: 371–375

    Article  CAS  PubMed  Google Scholar 

  • Rogers RD, Everitt BJ, Baldacchino A, Blackshaw AJ, Swainson R, Wynne K, Baker NB, Hunter J, Carthy T, Booker E, London M, Deakin JF, Sahakian BJ, Robbins TW (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryp-tophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20(4): 322–339

    Article  CAS  PubMed  Google Scholar 

  • Rothman RB, Mele A, Reid AA, Akunne HC, Greig N, Thurkauf A, de Costa BR, Rice KC, Pert A (1991) GBR12909 antagonizes the ability of cocaine to elevate extracellular levels of dopamine. Pharmacol Biochem Behav 40(2): 387–397

    Article  CAS  PubMed  Google Scholar 

  • Schlaepfer TE, Strain EC, Greenberg BD, Preston KL, Lancaster E, Bigelow GE, Barta PE, Pearlson GD (1998) Site of opioid action in the human brain: mu and kappa agonists’ subjective and cerebral blood flow effects. Am J Psychiatry 155: 470–473

    CAS  PubMed  Google Scholar 

  • Schultz W (2001) Reward signaling by dopamine neurons. Neuroscience 7: 293–302

    Article  CAS  Google Scholar 

  • van Dyck CH, Rosen MI, Thomas HM, McMahon TJ, Wallace EA, O’Connor PG, Sullivan M, Krystal JH, Hoffer PB, Woods SW, Kosten TR (1994) SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from bupre-norphine. Psychiatry Res 55(4): 181–191

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex 10(3): 318–325

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN, Vitkun S, Logan J, Gatley SJ, Pappas N, Hitzemann R, Shea CE (1997) Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 386: 827–830

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L, Ding Y, Gatley SJ, Gif ford A, Franceschi D (2001) Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 15;21(2): RC121

    CAS  Google Scholar 

  • Wang GJ, Volkow ND, Fowler JS, Cervany P, Hitzemann RJ, Pappas NR, Wong CT, Felder C (1999) Regional brain metabolic activation during craving elicited by recall of previous drug experiences. Life Sci 64(9): 775–784

    Article  CAS  PubMed  Google Scholar 

  • Wolf ME (1998) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog Neurobiol 54: 679–720

    Article  CAS  PubMed  Google Scholar 

  • Authors’ address: Prof. D. Nutt, Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, United Kingdom, e-mail: david.j.nutt@bris.ac.uk

    Google Scholar 

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© 2003 Springer-Verlag/Wien

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Nutt, D., Lingford-Hughes, A., Daglish, M. (2003). Future directions in substance dependence research. In: Neuropsychopharmacology. Journal of Neural Transmission. Supplementa, vol 64. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6020-6_6

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  • DOI: https://doi.org/10.1007/978-3-7091-6020-6_6

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83903-4

  • Online ISBN: 978-3-7091-6020-6

  • eBook Packages: Springer Book Archive

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