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Cocaine Reward and Locomotor Activity in C57BL/6J and 129/SvJ Inbred Mice and Their F1 Cross

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Abstract

Large individual differences exist among mice in their behavioral responses to drugs of abuse, and many of these differences have a substantial genetic basis. The creation of new animal models using recombinant DNA technology has provided new genetic tools for assessing the role of specific candidate genes in drug response. This study presents a characterization of cocaine activation and reward in the two strains used most commonly for production of knockout mice, C57BL/6J and 129/SvJ, and their outcrossed F1 offspring. Using conditioned place preference, the study demonstrates that there are large strain differences in spontaneous locomotor activity and in the rewarding effects of cocaine. The 129/SvJ strain is hypoactive and is very sensitive to the locomotor activating effects of cocaine but does not develop cocaine-conditioned place preference under conditions that yield significant place preference in C57BL/6J mice. These phenotypes are not inherited in a simple additive manner, but rather the F1 generation resembles the C57BL/6J progenitor strain for a number of the behaviors examined.

Section snippets

Animals and Drugs

C57BL/6J and 129/SvJ were obtained from Jackson Laboratories (Bar Harbor, ME, USA) and maintained in the animal colonies of the Molecular Genetics Section of NIDA/Division of Intramural Research (Baltimore, MD, USA). Animals were housed in groups of generally five or six animals per cage; food and water were freely available, and the mice were maintained on a 12 L : 12 D cycle (lights on at 0700 h), in accordance with guidelines of the American Association for Laboratory Animal Care. All

Spontaneous Locomotor Activity and Development of Habituation

The C57BL/6J strain and the C57 × 129 F1 animals are significantly more active than the 129/SvJ strain, with three times the total distance traveled in a 30-min period (Fig. 1A) [F(2, 20) = 40.02, p < 0.0001; Bonferroni–Dunn post hoc, p < 0.0001]. Because F1 mice are heterozygous at all loci for which their progenitor strains differ, their response is determined by both additive genetic effects and the nonadditive effects of dominance and genic interaction. If the genes influencing locomotor

Discussion

As this and previous studies have so thoroughly demonstrated, the genetic makeup of an animal can greatly influence a variety of behaviors, including response to drugs of abuse 5, 6, 12, 17, 18. The present study characterizes cocaine response in a previously uncharacterized mouse strain, 129/SvJ, as well as in the widely used C57BL/6J strain and in F1 animals derived from them. This characterization and future studies focusing on other pharmacological agents will lay the foundation for a

Acknowledgements

I thank Jennifer Mulle for assistance in the conditioned place preference experiments and Linda Roggio for animal breeding assistance.

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