Plasma and brain methamphetamine concentrations in neonatal rats

Abstract

d-Methamphetamine ( d-MA) treatment during the neonatal period has been shown to induce acoustic startle hyperreactivity and Morris maze spatial learning deficits, but not to significantly affect Cincinnati maze sequential learning. 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 representative of those used in previously published neurobehavioral studies. Plasma parameters showed few age and dose-frequency effects; however, brain concentrations showed more consistent age-dependent effects. Brain area under the concentration (AUC) values were consistently higher, regardless of dosing schedule, in offspring treated on postnatal day (P) 1 compared to those treated on P11. Previous results with the multiple-dose schedules have shown that Morris maze spatial learning deficits only occur in those exposed beginning 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 effects. The plasma concentrations obtained in rats are within the range for human MA abusers based on extrapolations from human low-dose values to those expected for heavy users.