BACKGROUND: Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother's health but also the developing fetus. To provide better insight into these risks, we performed the following experiments. METHOD: First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment. RESULTS: We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure. CONCLUSION: We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure.

Charles University Prague 3rd Faculty of Medicine Department of Normal Pathological and Clinical Physiology Ke Karlovu 4 120 00 Prague Czech Republic

Institute of Chemical Technology Technicka 5 Prague 166 28 Czech Republic

Institute of Chemical Technology Technicka 5 Prague 166 28 Czech Republic; Institute of Physiology AS CR v v i Videnska 1083 Prague 142 20 Czech Republic

Prague Psychiatric Center Ustavni 91 7 Prague 181 00 Czech Republic

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