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Methamphetamine conditioned place preference in adolescent mice: Interaction between sex and strain
Lewis Nunez Severino1,2,3, Andre B Toussaint1,4, Rachael M Langa1
1Department of Psychology, Hunter College, City University of New York, USA.
Journal of Psychopharmacology (Oxford, England)
|February 28, 2026
Summary
Methamphetamine rewarding effects in adolescent mice show significant sex and strain differences. Neural circuit responses in the nucleus accumbens and hippocampus varied, impacting behavioral sensitization.
Area of Science:
- Neuroscience
- Adolescent Pharmacology
- Behavioral Genetics
Background:
- Adolescent methamphetamine (METH) use is more prevalent in females than males.
- Rodent studies indicate sex differences in METH's reinforcing effects, but adolescent neural circuit responses remain understudied.
- Few studies have explored sex differences in the neural circuits underlying METH's effects during adolescence.
Purpose of the Study:
- To investigate sex differences in METH's rewarding effects in adolescent mice.
- To identify sex- and strain-dependent alterations in associated neural circuits.
- To examine METH's impact on two common mouse strains (129Sv/Ev and C57Bl/6) used for transgenic research.
Main Methods:
- Assessed METH-induced conditioned place preference (CPP) in adolescent male and female 129Sv/Ev and C57Bl/6 mice.
- Administered 1 mg/kg METH to induce CPP.
- Quantified c-Fos protein expression in the nucleus accumbens (NAc) and hippocampus (CA1) post-conditioning.
Main Results:
- C57Bl/6 females, but not males, exhibited METH-induced CPP.
- 129Sv/Ev males, but not females, showed METH-induced CPP.
- Both strains exhibiting CPP had increased c-Fos+ cells in the NAc and CA1 compared to controls.
- Behavioral sensitization was observed only in 129Sv/Ev males.
Conclusions:
- METH's rewarding effects in adolescent mice are dependent on both sex and genetic background.
- Neural and behavioral responses to METH result from an interaction between sex-specific and genetic factors.
- Findings will inform the selection of mouse strains for future METH research, particularly in genetically modified models.
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