Neurotoxicity in the adult rat following chronic exposure to methamphetamine

$2,638,252ZIAFY2025DANIH

National Institute On Drug Abuse

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Abstract

We used a self-administration (SA) model and RNA sequencing revealed extensive transcriptional changes in the prefrontal cortex, nucleus accumbens, dorsal striatum, and midbrain of SR and SS rats. Notably, we identified shared genes with consistent expression patterns across all four brain regionsâFos and Ahsp in SR rats, and Tet1, Cym, and Tmem30c in SS rats. We found that treatment with SCH23390 produced a significant, dose-dependent reduction in METH intake among compulsive rats. However, discontinuation of SCH23390 led to the re-emergence of compulsive METH-taking behavior in shock-resistant rats. Translationally, RNA sequencing revealed that CPEB4 polyadenylation mechanisms contribute to the behavioral phenotype of shock-sensitive rats. We also observed sex- and brain region-specific alterations in the expression of histone deacetylases. RNA sequencing further revealed marked sex-dependent differences in striatal gene expression between male and female rats that self-administered METH.

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