Profiling of methamphetamine-induced modifications of gene expression patterns in the mouse brain.

Recently described DNA microarray technology allows parallel screening of expression patterns and regulation of hundreds of thousands of genes. In the present study, we used a microarray to examine the gene expressions in the midbrains of mice sacrificed 24 h after completion of a 7-day treatment period consisting of a once-daily treatment with saline (SS), saline followed by a single 2 mg/kg of body weight dose of methamphetamine (METH) (S-METH), or repeated 2 mg/kg METH doses (M-METH) that produced sensitization and place preference (rewarding effect). We used the commercially available cDNA microarray. Approximately 80% of the assessed transcripts in the total brain reached the Affymetrix criteria for "present" and "changed," as well as displaying > or =1.5-fold differences in hybridization intensity difference values in a comparison of SS data to S-METH or M-METH data. S-METH gene expression changes were observed in both up- and down-regulation, with 13 transcripts upregulated and 13 downregulated, whereas the majority of M-METH gene expression changes were observed in down-regulation, with 5 transcripts upregulated and 21 downregulated. We identified several genes that altered expression in both the S-METH and M-METH groups: a transcription factor gene, cellular stress/molecular chaperones, and a cellular regulatory gene.