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bioRxiv · 10.64898/2026.06.20.733497

Methamphetamine-induced disruption of neuropeptide expression in mice

Harkany, T.·Hokfelt, T.·Hevesi, Z.·Boroczky, C.·Anidil Pathikkaran, N.·Papageorgiou, K.
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Abstract

Psychoactive and psychotoxic drugs are particularly harmful, if their use coincides with critical developmental windows of brain maturation. Methamphetamine is one such stimulant with developmental exposure increasing seizure susceptibility and long-term neuronal maladaptation in children. Nevertheless, the extent at which infant and adult vulnerability to methamphetamine could differ in time-course and severity remains incompletely understood. Here, we developed a method to monitor methamphetamine-induced hyperactivity in infant mice at high temporal resolution, differentiate it from a biphasic response in adults, and link it to activity changes in cortical areas executing goal-directed (escape) behaviors in infant subjects when using Fos expression as a molecular surrogate. Subsequently, we hypothesized that methamphetamine could alter the expression and cellular distribution of inhibitory neuropeptides, which, when co-released with fast neurotransmitters, could protect circuit plasticity by counteracting methamphetamine-induced hyperexcitability. Methamphetamine differentially altered somatostatin, cholecystokinin, and galanin expression in corticolimbic areas. These data suggest that methamphetamine can evoke age-specific neurocircuit modifications, at least in mice.

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Harkany, T., Hokfelt, T., Hevesi, Z., Boroczky, C., Anidil Pathikkaran, N., Papageorgiou, K.. 2026-06-25. Methamphetamine-induced disruption of neuropeptide expression in mice. https://doi.org/10.64898/2026.06.20.733497

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