Methamphetamine-Induced Depression of Monoamine Synthesis in the Rat: Development of Tolerance

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Abstract
Animals treated with high doses of amphetamine were used as a model of schizophrenia due to the similarities between the psychosis associated with this mental disorder and thus induced by chronic amphetamine abuse. When administered to naive rats in high doses, the amphetamine-like CNS stimulant methamphetamine produces drastic alterations in the neurochemical parameters of the neostriatal monoaminergic systems. These alterations are characterized by a decrease in the activities of the rate-limiting enzymes for dopamine and serotonin [5-hydroxytryptamine] synthesis, as well as a decrease in the concentrations of both neurotransmitters and their metabolites. Tolerance develops to these neurochemical effects when drug administration occurs in a pattern similar to that encountered during chronic amphetamine abuse. The neurochemical alterations produced by amphetamines in naive and tolerant animals differ widely. The administration of high doses of amphetamine-like central stimulants to naive rats may not be an appropriate model for studying the neurochemical changes associated with psychosis and amphetamine abuse.