title: Variability in paralimbic dopamine signaling correlates with subjective responses to d-amphetamine.
abstract: Subjective responses to psychostimulants vary, the basis of which is poorly understood, especially in relation to possible cortical contributions. Here, we tested for relationships between participants' positive subjective responses to oral d-amphetamine (dAMPH) versus placebo and variability in striatal and extrastriatal dopamine (DA) receptor availability and release, measured via positron emission tomography (PET) with the radiotracer (18)F-fallypride. Analyses focused on 35 healthy adult participants showing positive subjective effects to dAMPH measured via the Drug Effects Questionnaire (DEQ) Feel, Like, High, and Want More subscales (Responders), and were repeated after inclusion of 11 subjects who lacked subjective responses. Associations between peak DEQ subscale ratings and both baseline (18)F-fallypride binding potential (BPnd; an index of D2/D3 receptor availability) and the percentage change in BPnd post dAMPH (%ΔBPnd; a measure of DA release) were assessed. Baseline BPnd in ventromedial prefrontal cortex (vmPFC) predicted the peak level of High reported following dAMPH. Furthermore, %ΔBPnd in vmPFC positively correlated with DEQ Want More ratings. DEQ Want More was also positively correlated with %ΔBPnd in right ventral striatum and left insula. This work indicates that characteristics of DA functioning in vmPFC, a cortical area implicated in subjective valuation, are associated with both subjective high and incentive (wanting) responses. The observation that insula %ΔBPnd was associated with drug wanting converges with evidence suggesting its role in drug craving. These findings highlight the importance of variability in DA signaling in specific paralimbic cortical regions in dAMPH's subjective response, which may confer risk for abusing psychostimulants.
authors.affiliation: Department of Psychology, PMB 407817, Vanderbilt University, 2301 Vanderbilt Place, Nashville, TN 37240-7817, United States. Electronic address: christopher.t.smith@vanderbilt.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Smith
authors.affiliation: Department of Psychology, PMB 407817, Vanderbilt University, 2301 Vanderbilt Place, Nashville, TN 37240-7817, United States.
authors.forename: Linh C
authors.initials: LC
authors.lastname: Dang
authors.affiliation: Department of Psychology, PMB 407817, Vanderbilt University, 2301 Vanderbilt Place, Nashville, TN 37240-7817, United States; Department of Psychiatry, Vanderbilt University School of Medicine, 1601 23rd Ave South, Suite 3057, Nashville, TN 37212, United States.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
authors.affiliation: Department of Radiology, UAB School of Medicine, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kessler
authors.affiliation: Department of Psychology, PMB 407817, Vanderbilt University, 2301 Vanderbilt Place, Nashville, TN 37240-7817, United States; Department of Psychiatry, Vanderbilt University School of Medicine, 1601 23rd Ave South, Suite 3057, Nashville, TN 37212, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Zald
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D017448:Receptors, Dopamine D2; D003913:Dextroamphetamine; D004298:Dopamine
keywords: Dopamine; Insula; Ventral striatum; Ventromedial PFC; d-amphetamine