Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement
- PMID: 18003850
- PMCID: PMC6673312
- DOI: 10.1523/JNEUROSCI.3371-07.2007
Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement
Abstract
The value of rewards (natural rewards and drugs) is associated with dopamine increases in the nucleus accumbens and varies as a function of context. The prefrontal cortex has been implicated in the context dependency of rewards and in the fixated high value that drugs have in addiction, although the mechanisms are not properly understood. Here we test the hypothesis that the prefrontal cortex regulates the value of rewards by modulating dopamine increases in nucleus accumbens and that this regulation is disrupted in addicted subjects. We used positron emission tomography to evaluate the activity of the prefrontal cortex (measuring brain glucose metabolism with [18F]fluorodeoxyglucose) and dopamine increases (measured with [11C]raclopride, a D2/D3 receptor ligand with binding that is sensitive to endogenous dopamine) induced by the stimulant drug methylphenidate in 20 controls and 20 detoxified alcoholics, most of whom smoked. In all subjects, methylphenidate significantly increased dopamine in striatum. In ventral striatum (where the nucleus accumbens is located) and in putamen, dopamine increases were associated with the rewarding effects of methylphenidate (drug liking and high) and were profoundly attenuated in alcoholics (70 and 50% lower than controls, respectively). In controls, but not in alcoholics, metabolism in orbitofrontal cortex (region involved with salience attribution) was negatively associated with methylphenidate-induced dopamine increases in ventral striatum. These results are consistent with the hypothesis that the orbitofrontal cortex modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum and that disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects.
Figures
![Figure 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6673312/bin/zns0460741020001.gif)
![Figure 2.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6673312/bin/zns0460741020002.gif)
![Figure 3.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/6673312/bin/zns0460741020003.gif)
Similar articles
-
Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: implications in addiction.Am J Psychiatry. 1999 Jan;156(1):19-26. doi: 10.1176/ajp.156.1.19. Am J Psychiatry. 1999. PMID: 9892293
-
Predominance of D2 receptors in mediating dopamine's effects in brain metabolism: effects of alcoholism.J Neurosci. 2013 Mar 6;33(10):4527-35. doi: 10.1523/JNEUROSCI.5261-12.2013. J Neurosci. 2013. PMID: 23467368 Free PMC article.
-
Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: relevance to addiction.J Neurosci. 2005 Apr 13;25(15):3932-9. doi: 10.1523/JNEUROSCI.0433-05.2005. J Neurosci. 2005. PMID: 15829645 Free PMC article.
-
Corticostriatal circuitry and habitual ethanol seeking.Alcohol. 2015 Dec;49(8):817-24. doi: 10.1016/j.alcohol.2015.03.003. Epub 2015 May 14. Alcohol. 2015. PMID: 26059221 Free PMC article. Review.
-
Addiction: beyond dopamine reward circuitry.Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15037-42. doi: 10.1073/pnas.1010654108. Epub 2011 Mar 14. Proc Natl Acad Sci U S A. 2011. PMID: 21402948 Free PMC article. Review.
Cited by
-
Implications of neuroimaging findings in addiction.Psychoradiology. 2023 Apr 29;3:kkad006. doi: 10.1093/psyrad/kkad006. eCollection 2023. Psychoradiology. 2023. PMID: 38666116 Free PMC article. Review. No abstract available.
-
Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder.Front Genet. 2024 Apr 3;15:1345410. doi: 10.3389/fgene.2024.1345410. eCollection 2024. Front Genet. 2024. PMID: 38633406 Free PMC article.
-
Bridging Neuroscience and Clinical Assessment in a Patient with Alcohol Use Disorder, Anxiety, and Trauma.J Psychiatr Pract. 2024 Jan 1;30(1):62-67. doi: 10.1097/PRA.0000000000000763. J Psychiatr Pract. 2024. PMID: 38227730
-
A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study.PLoS One. 2024 Jan 11;19(1):e0296118. doi: 10.1371/journal.pone.0296118. eCollection 2024. PLoS One. 2024. PMID: 38206930 Free PMC article.
-
Neuronal-specific methylome and hydroxymethylome analysis reveal replicated and novel loci associated with alcohol use disorder.medRxiv [Preprint]. 2023 Nov 29:2023.11.28.23299094. doi: 10.1101/2023.11.28.23299094. medRxiv. 2023. Update in: Front Genet. 2024 Apr 03;15:1345410. doi: 10.3389/fgene.2024.1345410. PMID: 38105948 Free PMC article. Updated. Preprint.
References
-
- Bailey CP, Manley SJ, Watson WP, Wonnacott S, Molleman A, Little HJ. Chronic ethanol administration alters activity in ventral tegmental area neurons after cessation of withdrawal hyperexcitability. Brain Res. 1998;24:144–152. - PubMed
-
- Batel P, Pessione F, Maitre C, Rueff B. Relationship between alcohol and tobacco dependencies among alcoholics who smoke. Addiction. 1995;90:977–980. - PubMed
-
- Bierut LJ, Rice JP, Goate A, Hinrichs AL, Saccone NL, Foroud T, Edenberg HJ, Cloninger CR, Begleiter H, Conneally PM, Crowe RR, Hesselbrock V, Li TK, Nurnberger JI, Jr, Porjesz B, Schuckit MA, Reich T. A genomic scan for habitual smoking in families of alcoholics: Common and specific genetic factors in substance dependence. Am J Med Genet A. 2004;124:19–27. - PubMed
-
- Collins DL, Holmes CJ, Peters TM, Evans AC. Automatic 3-D model-based neuroanatomical segmentation. Hum Brain Mapp. 1995;3:190–208.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources