title: Exposure to chronic intermittent nicotine vapor induces nicotine dependence.
abstract: Animal models of drug exposure are important tools for the study of the neurobiological mechanisms of nicotine dependence and as preclinical models for medication development. There are few non-invasive animal models of nicotine exposure and currently there is no known animal model of second-hand exposure to nicotine. We hypothesized that chronic administration of nicotine vapors would produce blood levels of nicotine in rodents that are clinically relevant to those observed in human smoking and that rodents exposed to nicotine vapors would develop dependence to nicotine. We developed a system that vaporizes nicotine in the air in a stable, reliable and consistent manner. Intermittent exposure to nicotine vapor (0.2mg/m(3)) for 8 or 14h per day for 7days produced a concentration of nicotine in the blood of 22ng/mL. Sixteen hours after removal from nicotine vapors, rats showed significant somatic withdrawal signs precipitated by mecamylamine (1.5mg/kg). These results provide a new rodent model of nicotine dependence using vapor administration that produces consistent levels of nicotine in the blood that are relevant for both heavy smoking and second-hand smoking, using a non-invasive technique that mimics the intermittent aspect and route of administration in humans.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. ogeorge@scripps.edu
authors.forename: Olivier
authors.initials: O
authors.lastname: George
authors.forename: Taryn E
authors.initials: TE
authors.lastname: Grieder
authors.forename: Maury
authors.initials: M
authors.lastname: Cole
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000097:blood* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000097:blood* / Q000523:psychology
chemical_list: D009538:Nicotine