title: Impact of short access nicotine self-administration on expression of α4β2* nicotinic acetylcholine receptors in non-human primates.
abstract: Although nicotine exposure upregulates the α4β2* subtype of nicotinic acetylcholine receptors (nAChRs), the upregulation of nAChRs in non-human primates voluntarily self-administering nicotine has never been demonstrated.
  
  
  
  The objective of the study is to determine if short access to nicotine in a non-human primate model of nicotine self-administration is sufficient to induce nAChRs upregulation.
  
  
  
  We combined a nicotine self-administration paradigm with in vivo measure of α4β2* nAChRs using 2-[(18)F]fluoro-A-85380 (2-FA) and positron emission tomography (PET) in six squirrel monkeys. PET measurement was performed before and after intravenous nicotine self-administration (unit dose 10 μg/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (1 h daily per weekday) to nicotine was allowed for 4 weeks and levels of α4β2* nAChRs were measured 4 days later.
  
  
  
  This intermittent access was sufficient to induce upregulation of α4β2* receptors in the whole brain (31 % upregulation) and in specific brain areas (+36 % in amygdala and +62 % in putamen).
  
  
  
  These results indicate that intermittent nicotine exposure is sufficient to produce change in nAChRs expression.
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, Canada, M5S 2S1. bernard.lefoll@camh.ca.|Departments of Family and Community Medicine, Pharmacology, Psychiatry, Institute of Medical Sciences, University of Toronto, Toronto, Canada. bernard.lefoll@camh.ca.|Ambulatory Care and Structured Treatment Program, Centre for Addiction and Mental Health, Toronto, Canada. bernard.lefoll@camh.ca.|Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA. bernard.lefoll@camh.ca.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.|The Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Disease, NIH, Fort.Detrick, Frederick, MD, 21702, USA.
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Chefer
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.|Office of the Clinical Director (retired), Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.
authors.forename: Alane S
authors.initials: AS
authors.lastname: Kimes
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.affiliation: Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.affiliation: Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA.|Department Psychiatry and Behavioral Sciences and Center for Smoking Cessation, Duke University Medical Center, 2424 Erwin Road, Suite 201, Durham, NC, 27705, USA.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
mesh_terms: D000818:Animals; D001384:Azetidines / Q000032:analysis; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000032:analysis; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000032:analysis; D011978:Receptors, Nicotinic / Q000032:analysis / Q000096:biosynthesis*; D012646:Self Administration
chemical_list: C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine
keywords: In vivo binding; Nicotine self-administration; Non-human primates; Positron emission tomography