Changes in cholecystokinin mRNA expression in methamphetamine-induced behavioral sensitization.

Neuropeptide cholecystokinin (CCK) mRNA was measured in the rat brain subchronically treated with methamphetamine (MAP). Male Wistar rats were injected daily with MAP (3 or 6 mg/kg, i.p., once a day) or saline for 14 days. Progressive reinforcement was observed in MAP-induced stereotyped behaviors. After 7 or 14 days of discontinuation, the rats were decapitated and the brains were prepared for Northern blot analysis using 32P-labeled cDNA probes. Northern blot analysis revealed that the levels of CCK mRNA in the frontal cortex and the hippocampus of 3 or 6 mg/kg MAP-treated rats were significantly decreased, compared to the saline-treated controls. These findings indicate that the alteration in CCK mRNA levels in the frontal cortex and the hippocampus of MAP-treated rats persisted for at least 2 weeks and might be involved in the expression of MAP-induced long-lasting behavioral sensitization (reverse tolerance).