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Open AccessArticle

C57BL/6 Substrain Differences in Pharmacological Effects after Acute and Repeated Nicotine Administration

Department of Pharmacology and Toxicology, and Translational Research Initiative for Pain and Neuropathy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Takeda Pharmaceutical Company Limited, Cambridge, MA 02139, USA
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Department of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, ON, Canada
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Author to whom correspondence should be addressed.
Brain Sci. 2019, 9(10), 244;
Received: 3 September 2019 / Revised: 18 September 2019 / Accepted: 19 September 2019 / Published: 21 September 2019
Tobacco smoking is the major cause of disability and death in the United States and around the world. In addition, tobacco dependence and addiction express themselves as complex behaviors involving an interplay of genetics, environment, and psychological state. Mouse genetic studies could potentially elucidate the novel genes and/or gene networks regulating various aspects of nicotine dependence. Using the closely related C57BL/6 (B6) mice substrains, recent reports have noted phenotypic differences within C57BL/6J (B6J) and C57BL/6N (B6N) mice for some drugs of abuse: alcohol, opiates, and cocaine. However, the differences in nicotine’s effects have not yet been described in these substrains. We examined the phenotypic differences in these substrains following the acute and repeated administration of nicotine in several pharmacological measures, including locomotion (after acute and repeated exposure), body temperature, nociception, and anxiety-like behaviors. We report substrain differences in the pharmacological effects of acute and repeated nicotine administration in the B6 substrains. Overall, we show enhanced nicotine sensitivity to locomotion, hypothermia, antinociception, and anxiety-like behaviors in the B6J mouse substrain compared to B6N. In the repeated administration paradigm, both the B6N and B6J substrains showed no sensitized locomotor responses after repeated exposure to nicotine at the two doses tested. This study thus provides evidence that the B6 mouse substrains may be useful for genetic studies to elucidate some of the genetic variants involved in tobacco dependence and addiction. View Full-Text
Keywords: nicotine; acute effects; mice; C57BL/6 substrains nicotine; acute effects; mice; C57BL/6 substrains
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Akinola, L.S.; Mckiver, B.; Toma, W.; Zhu, A.Z.X.; Tyndale, R.F.; Kumar, V.; Damaj, M.I. C57BL/6 Substrain Differences in Pharmacological Effects after Acute and Repeated Nicotine Administration. Brain Sci. 2019, 9, 244.

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