To study the role of the preprotachykinin A (PPT) mRNA in methamphetamine (MAP)-induced behavioral sensitization, rats were daily injected within MAP (3 or 6 mg/kg, i.p., once a day) or saline for 14 days. Progressive enhancement was observed in MAP-induced stereotyped behavior. After 7 or 14 days of discontinuation of MAP treatment, the rats were decapitated and the brains were prepared for Northern blot analysis using a 32P-labeled oligonucleotide probe. Northern blot analysis revealed that the level of PPT mRNA in the striatum of 3 or 6 mg/kg MAP-treated rats was significantly decreased, compared to that in the saline-treated controls. These findings indicate that PPT mRNA expression plays an important role in MAP-induced long-lasting behavioral sensitization and dopamine hyperactivity.