Astrocytic Changes in the Striatum and Hippocampus in A Rat Model of Human Methamphetamine Abuse
DOI:
https://doi.org/10.48048/tis.2026.13366Keywords:
Methamphetamine, Striatum, Nucleus accumbens, Hippocampus, Astrocyte, Glial Fibrillary Acidic Protein, Astrogliosis, Immunohistochemistry, Methamphetamine, Striatum, Nucleus accumbens, Hippocampus, Astrocyte, Glial fibrillary acidic protein, Astrogliosis, ImmunohistochemistryAbstract
Methamphetamine (METH) is a highly addictive psychostimulant that exerts profound effects on the central nervous system, including psychosis, cognitive impairment, and memory disturbances. Chronic METH use disrupts neurotransmitter homeostasis and neuronal circuitry, contributing to long-term neurotoxicity. Astrocytes, as key regulators of synaptic transmission and brain homeostasis, are likely involved in METH-induced neuropathology. This study investigated astrocytic responses in specific brain regions, namely the striatum, nucleus accumbens, and hippocampus, using a rodent METH exposure paradigm that mimics human patterns of abuse. Immunohistochemical analysis of glial fibrillary acidic protein (GFAP) was performed in sham control, acute binge, escalating dose, and escalating dose-binge METH groups. Results showed increased GFAP immunoreactivity consistent with reactive astrogliosis, particularly in the escalating dose-binge group, suggesting heightened susceptibility in the striatum and hippocampus. Notably, region-specific astrocytic responses were observed: increased numbers of GFAP-positive cells without corresponding GFAP area expansion in the nucleus accumbens core, nucleus accumbens shell, and hippocampal CA2 subregion, suggesting a relatively mild astrocyte reactivity with limited cytoskeletal remodeling. In contrast, increased GFAP area without a corresponding increase in the number of GFAP-positive cells in the dorsolateral subregion of the striatum suggested features consistent with astrocytic hypertrophy or process elongation. These findings underscore the complementary roles of GFAP-positive cell counts and GFAP area in assessing astrogliosis. The observed profiles resemble those found in neurodegenerative and psychiatric disorders, raising the possibility of shared pathological mechanisms. Although functional outcomes were not directly assessed, these structural changes provide insight into METH-related brain alterations and highlight astrocytes as potential targets for therapeutic intervention.
HIGHLIGHTS
- METH exposure in rats induces reactive astrogliosis.
- Elevated astrogliosis reflects METH-induced neurotoxicity.
- Escalating dose-METH binge increases astrogliosis in striatum and hippocampus.
- Astrogliosis indicates a pathological correlate of psychosis and cognitive decline.
GRAPHICAL ABSTRACT
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