title: Guidelines on nicotine dose selection for in vivo research.
abstract: BACKGROUND
  This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure.
  
  
  OBJECTIVE
  This review capitalizes on the authors' collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models.
  
  
  RESULTS
  Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses.
  
  
  CONCLUSIONS
  The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Crowe 115, Memphis, TN 38163, USA. smatta@utmem.edu
authors.forename: Shannon G
authors.initials: SG
authors.lastname: Matta
authors.forename: David J
authors.initials: DJ
authors.lastname: Balfour
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Boyd
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Caggiula
authors.forename: Caroline R
authors.initials: CR
authors.lastname: Craig
authors.forename: Allan C
authors.initials: AC
authors.lastname: Collins
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Gardiner
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Grady
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
authors.forename: Sherry S
authors.initials: SS
authors.lastname: Leonard
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Lukas
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Marks
authors.forename: Sarah E
authors.initials: SE
authors.lastname: McCallum
authors.forename: Neeraja
authors.initials: N
authors.lastname: Parameswaran
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Maryka
authors.initials: M
authors.lastname: Quik
authors.forename: Jed E
authors.initials: JE
authors.lastname: Rose
authors.forename: Adrian
authors.initials: A
authors.lastname: Rothenfluh
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
authors.forename: Ian P
authors.initials: IP
authors.lastname: Stolerman
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Wehner
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zirger
mesh_terms: D000818:Animals; D035841:Behavioral Research / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D017408:Guidelines as Topic; D006801:Humans; D008954:Models, Biological; D009538:Nicotine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D013045:Species Specificity
chemical_list: D005731:Ganglionic Stimulants; D009538:Nicotine