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Methamphetamine Conditioned Place Preference in Adolescent Mice: Interaction Between Sex and Strain.

Lewis Nunez Severino, Andre B Toussaint, Rachael M Langa

    Biorxiv : the Preprint Server for Biology
    |December 3, 2025
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    Summary

    Methamphetamine

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    Area of Science:

    • Neuroscience
    • Addiction Research
    • Adolescent Psychology

    Background:

    • Adolescent methamphetamine use shows sex differences, with higher rates in females.
    • Rodent studies suggest sex differences in methamphetamine's reinforcing effects.
    • Limited research exists on sex differences in adolescent methamphetamine neural circuits.

    Purpose of the Study:

    • To investigate sex differences in methamphetamine's rewarding effects in adolescent mice.
    • To identify associated neural circuit changes in two common mouse strains.
    • To inform the selection of background strains in future genetic studies.

    Main Methods:

    • Conditioned place preference (CPP) test with 1mg/kg methamphetamine in adolescent male and female mice (129Sv/Ev and C57Bl/6 strains).
    • Quantification of c-Fos protein expression in the nucleus accumbens (NAc) and hippocampus (CA1) post-conditioning.
    • Behavioral sensitization assessment in specific groups.

    Main Results:

    • Methamphetamine-induced CPP was sex-dependent and strain-dependent.
    • C57Bl/6 females and 129Sv/Ev males exhibited CPP.
    • Increased c-Fos expression in NAc and CA1 correlated with CPP, suggesting enhanced NAc-CA1 communication.
    • Behavioral sensitization observed only in 129Sv/Ev males.

    Conclusions:

    • Methamphetamine's rewarding effects in adolescents are influenced by both sex and genetic background.
    • These findings highlight the interplay between sex-specific and genetic factors in drug response.
    • Results provide crucial data for selecting appropriate mouse strains in future research.