In 60- and 80-day-old rats, TH-positive terminal depletion occurred simultaneously with increased glial fibrillary acid protein (GFAP)-containing astrocytes in the caudate-putamen nucleus following four 10 or 20 mg/kg methamphetamine treatments. At 40 days, astrocytes were increased without depletion of TH-positive terminals. At younger ages (20 days old) neither marker was altered. Processes leading to methamphetamine-induced gliosis and TH-positive terminal depletion may not be present in rats prior to 40 and 60 days, respectively. The data suggest that factors other than degenerated dopaminergic terminals, such as increased glutamate release and/or production of free radicals may be involved in triggering striatal gliosis.