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 star ted. The aim of our study was to determine the effect of methamphetami ne (MAP)-induced behavioral sensitization ontogeny on MAP challenge-in duced 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 twic e 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 ac cording to the same schedule. Dialysis experiments were carried out 21 days after the last MAP or saline injection. All the rats were inject ed (IP) with a challenge dose of MAP (4 mg/kg). We reconfirmed that MA P-induced stereotyped behavior was enhanced significantly only when MA P pretreatment was started on PNDs 21, 28, and 56, but not PNDs 7 and 14. Correspondingly, the MAP challenge induced significantly greater i ncreases in striatal extracellular DA concentrations in the MAP-pretre ated rats compared with control rats only when MAP pretreatment was in itiated on PNDs 21, 28, and 56, but not in younger rats.