Guidelines on nicotine dose selection for in vivo research.
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.
Matta
Shannon G
SG
Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, 874 Union Avenue, Crowe 115, Memphis, TN 38163, USA. smatta@utmem.edu
Balfour
David J
DJ
Benowitz
Neal L
NL
Boyd
R Thomas
RT
Buccafusco
Jerry J
JJ
Caggiula
Anthony R
AR
Craig
Caroline R
CR
Collins
Allan C
AC
Damaj
M Imad
MI
Donny
Eric C
EC
Gardiner
Phillip S
PS
Grady
Sharon R
SR
Heberlein
Ulrike
U
Leonard
Sherry S
SS
Levin
Edward D
ED
Lukas
Ronald J
RJ
Markou
Athina
A
Marks
Michael J
MJ
McCallum
Sarah E
SE
Parameswaran
Neeraja
N
Perkins
Kenneth A
KA
Picciotto
Marina R
MR
Quik
Maryka
M
Rose
Jed E
JE
Rothenfluh
Adrian
A
Schafer
William R
WR
Stolerman
Ian P
IP
Tyndale
Rachel F
RF
Wehner
Jeanne M
JM
Zirger
Jeffrey M
JM
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
D005731:Ganglionic Stimulants; D009538:Nicotine