Age-related toxicity in prefrontal cortex and caudate-putamen complex of gerbils (Meriones unguiculatus) after a single dose of methamphetamine.

Single, intermediate to large doses (6-60 mg/kg) of methamphetamine were applied to study the acute neurotoxic effects in developing male gerbils (up to 24 months). A sensitive silver-staining method was used to analyze the toxicity of methamphetamine by light and electron-microscopy. It was shown that treatment with the drug degraded synaptic components, as well as a small population of neurones in the caudate-putamen complex accompanied by accumulation of lysosomes in fibers and axon terminals. In juveniles, methamphetamine in doses of 25-60 mg/kg, resulted in accumulation of lysosomes, selectively in the prefrontal cortex. In young adults, only about half of these doses were sufficient to produce consistent and/or additional effects in the caudate-putamen complex. When the gerbils grew older than 8 months, treatment with drug led to accumulation of lysosomes, exclusively in the caudate-putamen, with acute doses ranging from 6 to 12 mg/kg. Acute neurotoxicity with methamphetamine has thus been induced by doses, which hitherto have been claimed to produce behavioural sensitization. Since dopamine (DA) seems the most likely transmitter to be affected, age-related differences in methamphetamine-induced neurotoxicity are discussed in relation to the background of developing DA-response systems, which are still changing in pattern during ageing.