1. Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects.
- Author
-
Adinoff B, Devous MD, Williams MJ, Harris TS, Best SE, Dong H, and Zielinski T
- 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
- 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., (Published 2012. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2014
- Full Text
- View/download PDF