Ontogeny of enhanced striatal dopamine release in rats with methamphetamine-induced behavioral sensitization

The behavioral sensitization has not been observed in rats under three weeks of age when administration of repeated psychostimulants is started. The aim of our study was to determine the effect of methamphetamine (MAP)-induced behavioral sensitization ontogeny on MAP challenge-induced changes of striatal extracellular concentrations of dopamine (DA) and its metabolites, using in vivo microdialysis. Experimental rats aged 7, 14, 21, 28, and 56 postnatal days (PNDs) were injected IP twice daily with 2 mg/kg MAP for three days, followed by 4 mg/kg for three days. Matched control rats were given equivalent volumes of saline according to the same schedule. Dialysis experiments were carried out 21 days after the last MAP or saline injection. All the rats were injected (IP) with a challenge dose of MAP (4 mg/kg). We reconfirmed that MAP-induced stereotyped behavior was enhanced significantly only when MAP pretreatment was started on PNDs 21, 28, and 56, but not PNDs 7 and 14. Correspondingly, the MAP challenge induced significantly greater increases in striatal extracellular DA concentrations in the MAP-pretreated rats compared with control rats only when MAP pretreatment was initiated on PNDs 21, 28, and 56, but not in younger rats.