title: Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects.
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.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA VA North Texas Health Care System, Dallas, TX, USA Nuclear Medicine Center and Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA University of Texas School of Public Health, Dallas, TX, USA.
authors.forename: Bryon
authors.initials: B
authors.lastname: Adinoff
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Williams
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harris
authors.forename: Susan E
authors.initials: SE
authors.lastname: Best
authors.forename: Hongyun
authors.initials: H
authors.lastname: Dong
authors.forename: Tanya
authors.initials: T
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects; D006801:Humans; D008297:Male; D017294:Ondansetron / Q000494:pharmacology*; D020534:Parahippocampal Gyrus / Q000098:blood supply / Q000187:drug effects; D010555:Personality Inventory; D019275:Radiopharmaceuticals; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012965:Sodium Chloride / Q000008:administration & dosage; D020531:Subthalamic Nucleus / Q000098:blood supply / Q000187:drug effects; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D019690:Technetium Tc 99m Exametazime; D012965:Sodium Chloride; D017294:Ondansetron