Advance Access publication June 10, 2009 Vulnerability to (þ)-Methamphetamine Effects and the Relationship to Drug Disposition in Pregnant Rats during Chronic Infusion

Chronic (1)-methamphetamine (METH) use during pregnancy increases the health risk for both mother and fetus. To provide insights into these risks, the relationship between changes in METH disposition and METH-induced pharmacological effects were studied in Sprague-Dawley rat dams and litters. Timed-pregnant rats (n 5 5–6) were given saline or METH (5.6–17.8 mg/ kg/day) by continuous sc infusion from gestational day (GD) 7 (before organogenesis) until GD21 (0–2 days before delivery). By GD11, all rats in the 17.8-mg/kg/day group died or were sacrificed for humane reasons. There were significant (p < 0.05) dose- and gestational time-dependent decreases in maternal body weight in the 10- to 13.2-mg/kg/day groups, which slowly recovered to near normal by GD21. Continued METH dosing in the surviving groups did not affect the mean pups/litter weight at the end of the experiment on GD21. While maternal and fetal METH an