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Neurotoxic effect of high dose methamphetamine administration on the hippocampal formation of adult mice:
K Shishido1, T Shishido, K Kato
1Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima City, Japan.
Abstract:
The volume of the hippocampal formation was measured after repeated methamphetamine (MAP) administration. MAP (30 mg/kg, i.p.) or an equivalent volume of saline (SAL) was administered once daily for 5 days to adult male BALB/c mice. The animals were perfused 7 days after the last injection, and brain sections were stained with cresyl violet and studied with a computer-assisted image analyzer. The volume of the molecular layer at the ventral position of the dentate gyrus of MAP-treated animals was significantly decreased (77% of control, p < 0.001). In contrast, the volumes of the molecular layers at the dorsal and midseptal positions of the dentate gyrus did not change after MAP administration. Similarly, repeated MAP treatment did not affect the volumes of the granular layer and hilus at the dorsal, midseptal or ventral positions of the dentate gyrus. The present results are the first to document a persistent neurotoxic effect of high dose MAP administration on the hippocampal volume of adult mice.
Insights
Repeated high-dose methamphetamine (MAP) administration caused significant volume reduction in the ventral dentate gyrus molecular layer in adult mice. This study reveals a persistent neurotoxic effect of MAP on hippocampal volume.
Area of Science:
- Neuroscience
- Toxicology
- Neuroanatomy
Background:
- Methamphetamine (MAP) is a psychostimulant drug with known neurotoxic potential.
- Previous research indicates MAP can affect brain structures, but its specific impact on hippocampal subregions requires further investigation.
Purpose of the Study:
- To investigate the long-term effects of repeated high-dose methamphetamine administration on the volume of the hippocampal formation in adult mice.
- To determine if MAP-induced neurotoxicity is region-specific within the dentate gyrus.
Main Methods:
- Adult male BALB/c mice received daily intraperitoneal injections of MAP (30 mg/kg) or saline for 5 consecutive days.
- Animals were perfused 7 days after the last injection.
- Brain sections were stained and analyzed using a computer-assisted image analyzer to measure hippocampal subregion volumes.
Main Results:
- Repeated MAP administration significantly decreased the volume of the molecular layer at the ventral position of the dentate gyrus (77% of control, p < 0.001).
- No significant changes were observed in the volumes of the molecular layers at dorsal and midseptal positions.
- Volumes of the granular layer and hilus across all positions (dorsal, midseptal, ventral) remained unaffected by MAP treatment.
Conclusions:
- High-dose, repeated methamphetamine administration induces a persistent, region-specific neurotoxic effect on the ventral dentate gyrus molecular layer in adult mice.
- These findings provide the first evidence of MAP-induced volume reduction in this specific hippocampal subregion.