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Nicotine & Tobacco Research Advance Access originally published online on May 29, 2009
Nicotine & Tobacco Research 2009 11(7):851-858; doi:10.1093/ntr/ntp076
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Sex differences in response to nicotine in C57Bl/6:129SvEv mice

Carolina Isiegas, Stephen D. Mague and Julie A. Blendy

Carolina Isiegas, Ph.D., Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA
Stephen D. Mague, B.A., Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA
Julie A. Blendy, Ph.D., Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA

Corresponding Author: Julie A. Blendy, Department of Pharmacology, 2211 Translational Research Laboratories, University of Pennsylvania School of Medicine, 125 South 31st Street, Philadelphia, PA 19104, USA. Telephone: 215-898-0730; Fax: 215-573-2041; E-mail: blendy{at}mail.med.upenn.edu


  Abstract

Introduction: Human studies suggest that smoking behavior in men may depend more on the pharmacological effects of nicotine, whereas in women, this behavior may rely more on nonpharmacological factors associated with smoking. Investigation of these parameters in mice may also reveal sex differences.

Methods: Male and female C57Bl/6:129SvEv hybrid mice were exposed to increasing concentrations of nicotine in a voluntary oral nicotine consumption paradigm in which we measured fluid consumption over time and dose. Separate cohorts of mice were exposed to nicotine in a place-conditioning paradigm, and preference was determined. These behavioral models were used to examine sex differences in mice as they rely on pharmacological as well as nonpharmacological factors. Mice exposed to nicotine or saline also were tested for sex differences in locomotor-activating effects of nicotine and in analgesia using standard activity monitoring and hot-plate tests.

Results: Females responded more to the conditioned rewarding effects of nicotine compared with males. Males, however, seemed more responsive to the pharmacological aspects of nicotine by reducing nicotine drinking at higher concentrations; females maintained consistent levels of intake over several doses of nicotine. Male and female mice demonstrated similar locomotor and antinociceptive responses to nicotine.

Discussion: These data suggest that place-conditioning and two-bottle choice paradigms may be more sensitive measures of sexual dimorphism in the C57BL/6:129SvEv hybrid mouse than are locomotor or nociception assays.

Received: October 20, 2008; Accepted: March 23, 2009

Present address: Carolina Isiegas, Centro de Investigaciones Biologicas, Madrid, Spain.


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