TRANSPLACENTAL COCAINE EXPOSURE-1 - A RODENT MODEL

To characterize the transplacental effects of cocaine on the developin g brain, we have developed a mouse model of gestational cocaine exposu re. Pharmacokinetic analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found in fetal brain and plasma at 30 and 120 min following SC administration to embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice daily with cocaine HCl at 20 mg/kg SC from gestational day ES to E17 (()C) demonstrated less foo d intake and lower percentage weight gain than vehicle-injected dams a llowed access to food ad lib (SAL). A nutritionally paired control gro up of dams injected with saline vehicle and pair-fed with the COC dams (SPF) demonstrated the lowest percentage weight gain of all three gro ups. The surrogate fostered offspring of COC and SPF darns demonstrate d persistent growth retardation [on postnatal days (P) 1, P9, and P50] and transient brain growth retardation ton P1 and P9) when compared t o pups born to SAL dams. We conducted behavioral tests that allowed us to dissociate the indirect effect of cocaine-induced malnutrition fro m a direct effect of prenatal cocaine administration in altering postn atal behavior. Pups from all three groups were tested for first-order Pavlovian conditioning on P9 or P12, or for the ability to ignore redu ndant information in a blocking paradigm on P50 or P100. Unlike the SP F and SAL controls, COC mice (i.e., mice born to COC dams) were unable to acquire an aversion to an odor previously paired with shock on P9. This learning deficit was transient because on P12, COC mice trained on the same conditioning task displayed an aversion to the odor that w as indistinguishable from the SPF and SAL controls. P50 and P100 COC m ice land to a lesser extent, SPF mice) demonstrated a persistent behav ioral deficit in the blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent mo del have developmental implications for human infants exposed to cocai ne in utero. (C) 1998 Elsevier Science Inc.