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Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects.
- Source :
-
Addiction biology [Addict Biol] 2014 Mar; Vol. 19 (2), pp. 250-61. Date of Electronic Publication: 2012 Mar 28. - Publication Year :
- 2014
-
Abstract
- 5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self-administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched healthy control participants. Differences between early- (first use before 20 years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine-addicted and control participants were observed following ondansetron relative to saline. Early-onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late-onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/hippocampal gyrus. Early-onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late-onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine-addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol-dependent patients.<br /> (Published 2012. This article is a U.S. Government work and is in the public domain in the USA.)
- Subjects :
- Adult
Age of Onset
Case-Control Studies
Cocaine-Related Disorders diagnostic imaging
Female
Functional Neuroimaging methods
Hippocampus drug effects
Humans
Male
Parahippocampal Gyrus blood supply
Parahippocampal Gyrus drug effects
Personality Inventory
Radiopharmaceuticals
Receptors, Serotonin, 5-HT3 drug effects
Receptors, Serotonin, 5-HT3 physiology
Sodium Chloride administration & dosage
Subthalamic Nucleus blood supply
Subthalamic Nucleus drug effects
Technetium Tc 99m Exametazime
Tomography, Emission-Computed, Single-Photon methods
Young Adult
Cerebrovascular Circulation drug effects
Cocaine-Related Disorders physiopathology
Hippocampus blood supply
Ondansetron pharmacology
Regional Blood Flow drug effects
Serotonin Antagonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1369-1600
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Addiction biology
- Publication Type :
- Academic Journal
- Accession number :
- 22458709
- Full Text :
- https://doi.org/10.1111/j.1369-1600.2012.00450.x