title: The effects of chronic alcohol self-administration on serotonin-1A receptor binding in nonhuman primates.
abstract: BACKGROUND
  Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [(18)F]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naïve and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding.
  
  
  METHODS
  Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [(18)F]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [(18)F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed.
  
  
  RESULTS
  Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels.
  
  
  CONCLUSIONS
  The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration.
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States. Electronic address: ansel.hillmer@yale.edu.
authors.forename: Ansel T
authors.initials: AT
authors.lastname: Hillmer
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States.
authors.forename: Dustin W
authors.initials: DW
authors.lastname: Wooten
authors.affiliation: Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Dana L
authors.initials: DL
authors.lastname: Tudorascu
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison, WI, United States.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States.
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Ahlers
authors.affiliation: Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, United States; Department of Kinesiology, University of Wisconsin, Madison, WI, United States.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Resch
authors.affiliation: Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, United States; Department of Kinesiology, University of Wisconsin, Madison, WI, United States.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Larson
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Converse
authors.affiliation: Department of Psychology, University of Wisconsin, Madison, WI, United States; Department of Psychology, Montana State University, Bozeman, MT, United States.
authors.forename: Colleen F
authors.initials: CF
authors.lastname: Moore
authors.affiliation: Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, United States; Department of Kinesiology, University of Wisconsin, Madison, WI, United States; Department of Psychology, University of Wisconsin, Madison, WI, United States.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Schneider
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States; Department of Psychiatry, University of Wisconsin, Madison, WI, United States.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012646:Self Administration
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D000431:Ethanol
keywords: 5-HT1A; Chronic alcohol self-administration; PET imaging; Rhesus monkey; Serotonin