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• W4377029042 abstract "<b>Abstract ID 23437</b> <b>Poster Board 136</b> Methamphetamine misuse is a growing health crisis devastating the lives of millions throughout the world. Decades of research has focused on modulating the mesolimbic dopamine pathway as a target for methamphetamine medications development due to the known rewarding and reinforcing effects, yet no treatment is presently available. Recent evidence, however, indicates that methamphetamine induces widespread neuroinflammation which has been linked to both neurovascular damage and dopamine dysregulation. The aim of this research is to investigate a broadened neuropathology in an established model of methamphetamine binge dosing known to produce substantial and sustained dopamine dysregulation. For this study, we administered four intraperitoneal injections spaced two hours apart. Neurocognitive effects on learning and memory were assessed by passive avoidance assay and cerebral perfusion was evaluated using laser speckle contrast analysis (LASCA). Five days after the dosing regimen, we collected brain tissue for postmortem analysis which included high performance liquid chromatography (HPLC), quantitative polymerase chain reaction, and western blot analysis. HPLC analysis revealed that the dosing regimen induced a more than two-fold decrease in striatal dopamine levels when compared to saline controls. Methamphetamine exposed animals showed an absolute change in latency from training to testing in the passive avoidance assay that was fifty percent lower than that of control animals. Significant upregulation of gene expression of the cytokine interleukin 1 beta and the chemokine monocyte chemoattractant protein 1 was observed in striatal tissues obtained from mice administered methamphetamine. LASCA revealed a slight decrease in cerebral perfusion acutely following a bolus injection of MA; however, an increase in perfusion was detected one hour following the dosing regimen. Although much is known about the effects of dopamine and its dysregulation in the context of methamphetamine addiction, the role of extended neuropathology is understudied. Together the data presented here demonstrate that the binge dose regimen produces significant decreases in striatal dopamine and related cognitive deficits consistent with well-known effects of MA, and furthermore elucidates neurovascular damage and associated neuroinflammation not as frequently explored. These studies were supported by the Louisiana Addiction Research Center, the Center of Biomedical Research Excellence in Redox Biology and Cardiovascular Disease (P20GM121307), and an RO1 (R01NS120676) to KSM and a Multidisciplinary Training in Cardiovascular Pathophysiology fellowship through the Center for Cardiovascular Diseases and Sciences (T32HL155022) to NMH." @default.
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• W4377029042 date "2023-05-18" @default.
• W4377029042 modified "2023-09-29" @default.
• W4377029042 title "Dopamine Dysregulation and Beyond: Exploring Methamphetamine-Induced Neuropathology" @default.
• W4377029042 doi "https://doi.org/10.1124/jpet.122.234370" @default.
• W4377029042 hasPublicationYear "2023" @default.
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