title: Verbal memory and 5-HT1A receptors in healthy volunteers--A PET study with [carbonyl-(11)C]WAY-100635.
abstract: The serotonin 5-HT1A receptor is a putative drug development target in disorders with cognitive and in particular memory deficits. However, previous human positron emission tomography (PET) studies on 5-HT1A receptor binding and memory functions have yielded discrepant results. We explored the association between verbal memory and 5-HT1A receptor binding in 24 healthy subjects (14 male, 10 female, aged 18-41 years). The cognitive tests included the Wechsler Memory Scale-Revised (WMS-R), Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wisconsin Card Sorting Test (WCST). 5-HT1A receptor binding was measured with PET and the radioligand [carbonyl-(11)C]WAY-100635, which was quantified with the gold standard method based on kinetic modeling using arterial blood samples. We found that global 5-HT1A receptor binding was positively correlated with measures of verbal memory, such that subjects who had higher receptor binding tended to have better verbal memory than subjects who had lower receptor binding. Regional analyses suggested significant correlations in multiple neocortical brain regions and the raphe nuclei. We did not find significant correlations between 5-HT1A receptor binding and executive functions as measured with WCST. We conclude that neocortical as well as raphe 5-HT1A receptors are involved in verbal memory function in man.
authors.affiliation: Department of Adolescent Psychiatry, Päijät-Häme Central Hospital, Lahti, Finland.
authors.forename: Jani
authors.initials: J
authors.lastname: Penttilä
authors.affiliation: Department of Radiology, University of Turku, Turku, Finland; Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland; Department of Psychiatry, University of Turku, Turku, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Tuominen
authors.affiliation: Department of Psychiatry, University of Turku, Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Lumme
authors.affiliation: Department of Psychiatry, University of Turku, Turku, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Ilonen
authors.affiliation: Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.affiliation: Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland; Department of Psychiatry, University of Turku, Turku, Finland. Electronic address: jahi@utu.fi.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D014706:Verbal Learning / Q000502:physiology; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: 5-HT(1A) receptor; Imaging; Memory; Positron emission tomography; Serotonin