Abstract
Methamphetamine (MA) abuse remains a public health issue. Prenatal MA exposure (PME) poses a significant health problem, as we know very little about the drug's long-term physiological impact on the developing human brain. We investigated the long-term consequences of early MA exposure using a mouse model that targets the brain growth spurt, which occurs during human third-trimester. Adult mice previously subjected to acute MA during post-natal days 4–9 exhibited hyperactivity during the Open-Field Test, while exhibiting no motor coordination changes during the Rotarod Test. Neonatal MA exposure reduced basal dopamine (DA) uptake rates in adult nucleus accumbens slices compared with saline-injected controls. Although slices from neonatal MA-exposed mice showed no change in evoked DA signals in the presence of MA, they exhibited potentiated non-evoked DA release through DA efflux in response to MA. These data suggest that developmental MA exposure alters brain development to produce long-lasting physiological changes to the adult mesolimbic DA system, as well as altering responses to acute MA exposure in adulthood. This study provides new insights into an important, under-investigated area in drugs of abuse research.
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The datasets supporting the conclusions of this article are included within the article and its additional files.
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Acknowledgements
The authors wish to thank Ann Hashimoto and for technical assistance.
Funding
This work was supported by the National Institutes of Health [Grant Numbers R24 DA027318, P20-RR016467, G12MD007601, and F32 DK124963].
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FPB, DJT, and MAA designed the research; DJT performed the research; DJT, JTY and FPB analyzed the data; DJT and FPB wrote the manuscript; MAA and JTY were involved in manuscript revisions.
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All mouse care and experimental procedures were approved by the UH Manoa Institutional Animal Care and Use Committee (IACUC) and conducted in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals.
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Torres, D.J., Yorgason, J.T., Andres, M.A. et al. Methamphetamine Exposure During Development Causes Lasting Changes to Mesolimbic Dopamine Signaling in Mice. Cell Mol Neurobiol 42, 2433–2438 (2022). https://doi.org/10.1007/s10571-021-01120-4
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DOI: https://doi.org/10.1007/s10571-021-01120-4