SELECTIVE EFFECTS OF BEHAVIORALLY ACTIVE DOSES OF METHAMPHETAMINE ON MESSENGER-RNA EXPRESSION IN THE GERBIL BRAIN

Administration of methamphetamine results in neuronal damage that may be mediated through the production of oxygen-free radicals and modulations in levels of calcium and glutamate in the brain. These changes have been associated with alterations in gene expression, which may play a role in cell damage. To assess the differences in gene expression related to treatment with methamphetamine, levels of mRNA were evaluated for the proto-oncogene c-fos, heat-shock protein (HSP 70) and actin. It was found that c-fos mRNA expression increased in a dose-dependent manner after administration of methamphetamine. Whereas, levels of HSP mRNA dropped at small doses of methamphetamine and increased dramatically at large doses. In addition, both c-fos and HSP mRNA showed increased levels throughout the brain. Actin mRNA expression was unaffected by any dose of the drug. At the doses that altered gene expression, methamphetamine produced dose-related behavioral changes. Spontaneous locomotor activity was increased at 1.0 mg/kg of methamphetamine, while, larger doses did not alter activity. The data demonstrated that effects of methamphetamine on gene expression occurred within the behaviorally-active dose range and might correlate with the degree of neuronal damage. Selective modulation of gene expression may have a role in determining the acute quantitative and qualitative effects of methamphetamine and the long-term changes that occur after administration of methamphetamine.