The aim of the present study was to investigate a causal relationship between low-dose methamphetamine-induced (METH; 2 mg/kg, i.p. once every other day for 7 days) behavioral sensitization and memory function. We first investigated the spatial working memory (short-term memory) and long-term memory in mice behaviorally sensitized by repeated METH treatments. We also assessed changes in NMDA receptor binding in METH-treated mice. Acute METH administration induces hyperlocomotion but do not induce memory impairment of changes in NMDA receptor binding. However, repeated METH treatment in mice produced behavioral sensitization and showed memory impairment and a decrease in NMDA receptor binding in the prefrontal cortex, as well as in the CA1, CA2, and CA3 regions of the hippocampus. These results suggest that repeated METH-induced behavioral sensitization may be accompanied by memory impairment, characterized by decreased NMDA receptor binding in the prefrontal cortex and hippocampus. Our study shows clearly that repeated but not acute low dose METH treatment induces memory impairment in mice and the possible mechanism involves reduction of NMDA receptor binding in specific brain regions associated with learning and memory.
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