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Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration were investigated. We confirmed that reverse tolerance in stereotyped behavior was constructed up to the 28th day after repeated intermittent pretreatment with increasing doses of MAP (2.5, 5, and 7.5 mg/kg x 3 and 10 mg/kg x 2, every other day). During acoustic stimulation, locomotor activity in the saline group was significantly increased, but the activity after the stimulation was completely suppressed. In contrast to the saline group, locomotor activity was not influenced by the acoustic stimulation in the MAP group, suggesting that behavioral hyporesponsiveness to acoustic stimulation was induced by MAP treatment. Two days after the last injection, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyphenylacetic acid (5-HIAA) in the cerebral cortex, midbrain + thalamus, hypothalamus and striatum were significantly decreased. These changes were maintained up to the 28th day after the drug withdrawal in the cerebral cortex and the midbrain + thalamus. From these results, the persistence of behavioral hyporesponsiveness to acoustic stimulation might be associated with long-lasting reduction of 5-HT synthesis.

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Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration.