Plasma and brain methamphetamine concentrations neonatal rats

D-Methamphetamine (D-MPI) treatment during the neonatal period has been sho wn to induce acoustic startle hyperreactivity and Morris maze spatial learn ing deficits, but not to significantly affect Cincinnati maze sequential le arning. In order to characterize the internal dose in these experiments, MA was measured in plasma and brain of neonatal rats at one of two ages, and using one of three dose schedules, two of which were selected to be represe ntative of those used in previously published neurobehavioral studies. Plas ma parameters showed few age and dose-frequency effects; however, brain con centrations showed more consistent age-dependent effects. Brain area under the concentration (AUC) values were consistently higher, regardless of dosi ng schedule, in offspring treated on postnatal day (P) 1 compared to those treated on P11. Previous results with the multiple-dose schedules have show n that Morris maze spatial learning deficits only occur in those exposed be ginning on P11, whereas acoustic startle hyperreactivity is associated with exposure beginning on either P1 or P11. The pharmacokinetic parameters did not predict the long-term spatial learning and memory effects of neonatal MA administration, nor are they well correlated to the acoustic startle eff ects. The plasma concentrations obtained in rats are within the range for h uman MA abusers based on extrapolations from human low-dose values to those expected for heavy users. (C) 2001 Elsevier Science Inc. All rights reserv ed.