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Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption

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Abstract

Rationale

Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption.

Objectives

Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA.

Methods

Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA.

Results

Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood.

Conclusions

Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption.

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Acknowledgements

This work was supported by grants from NIDA (P50 DA018165 and T32 DA07262) and by the Department of Veterans Affairs. We are grateful to John Belknap for providing statistical software for performance of heritability calculations. All experiments were conducted in compliance with current laws in the United States of America.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, and Veterans Affairs Medical Center, Portland, OR, USA

    Angela C. Scibelli, Carrie S. McKinnon, Cheryl Reed, Sue Burkhart-Kasch, Na Li, Harue Baba, Jeanna M. Wheeler & Tamara J. Phillips

  2. Portland VA Medical Center, 3710 SW US Veterans Hospital Rd., R&D-32, Portland, OR, 97239, USA

    Tamara J. Phillips

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  1. Angela C. Scibelli
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  2. Carrie S. McKinnon
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  3. Cheryl Reed
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  4. Sue Burkhart-Kasch
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  5. Na Li
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  6. Harue Baba
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  7. Jeanna M. Wheeler
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  8. Tamara J. Phillips
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Correspondence to Tamara J. Phillips.

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Scibelli, A.C., McKinnon, C.S., Reed, C. et al. Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption. Psychopharmacology 214, 791–804 (2011). https://doi.org/10.1007/s00213-010-2086-2

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  • DOI: https://doi.org/10.1007/s00213-010-2086-2

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