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

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

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)791-804
Number of pages14
JournalPsychopharmacology
Volume214
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • Addiction
  • Clearance
  • Drinking
  • Heritability
  • Locomotor activity
  • Potassium chloride
  • Quinine
  • Reward
  • Saccharin
  • Stimulation

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption'. Together they form a unique fingerprint.

  • Cite this

    Scibelli, A. C., McKinnon, C. S., Reed, C., Burkhart-Kasch, S., Li, N., Baba, H., Wheeler, J. M., & Phillips, T. J. (2011). Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption. Psychopharmacology, 214(4), 791-804. https://doi.org/10.1007/s00213-010-2086-2