Future directions in substance dependence research
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.
KeywordsOrbitofrontal Cortex Substance Dependence Brain Circuit Glucose Metabolic Rate Emotional Salience
Unable to display preview. Download preview PDF.
- 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): 798–809PubMedCrossRefGoogle 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: 664–670PubMedCrossRefGoogle 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): 1640–1645PubMedCrossRefGoogle Scholar
- Malizia AL (2002) The neuroinaging of anxiety. In: Nutt DJ, Ballenger J (eds) Anxiety disorders. Blackwells, pp 201–228Google 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): 9–15Google 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): 322–339PubMedCrossRefGoogle 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): RC121Google Scholar
- Authors’ address: Prof. D. Nutt, Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, United Kingdom, e-mail: firstname.lastname@example.org Google Scholar