Effect of Methamphetamine Exposure During Prenatal and Preweaning Periods Lasts for Generations in Rats Romana  Slamberova ´ Marie Pometlova ´ Richard Rokyta Department of Normal Pathological and Clinical Physiology Third Faculty of Medicine Charles University in Prague Prague, Czech Republic E-mail: rslamber@lf3.cuni.cz ABSTRACT: Our previous studies demonstrated that methamphetamine (MA) administration during gestation and/or lactation affects maternal behavior in rats and that birth weight and sensory-motor coordination of their pups are also influenced. The present study tested the hypothesis that the effect of MA induces long-term changes affecting second generation of rats that were not exposed to the drug. Adult females exposed during prenatal and preweaning periods to 5 mg/kg MA daily, were examined for regularity of estrous cycle and mated with stimulus, unexposed males. Dams (nontreated absolute control, saline- and MA-exposed) were observed with their pups in two tests of maternal behavior (observational and retrieval tests). Their pups were further tested throughout the preweaning period to examine their development. Our data demonstrate that MA-exposed mothers displayed more nursing, were more often in the nest and in contact with their pups, and were faster in retrieving their pups than saline-exposed and/or control mothers. There were no differences in litter characteristics, birth weight and weight gain of pups between groups. Interestingly, pups from mothers exposed to MA during prenatal and preweaning period had impaired sensory-motor coordination. They achieved righting reflex in mid-air later than both control groups. Additionally, they had more falls in rotarod and bar-holding tests than pups from both control and saline-exposed mothers. In homing performance, pups from MA- and saline- exposed dams learned slower to return to the home box than pups from control dams. Thus, the present study demonstrates that MA abused by mothers may affect two generations of their offspring. ß 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 312–322, 2007. Keywords: methamphetamine; generation; maternal behavior; development; sensory-motor coordination; homing INTRODUCTION Family life affects development, behavior, and predis- position to some diseases of each individual is consider- able. Physical and emotional deprivation and family conflicts may induce long-term consequences in postnatal development of a child (Bifulco, Brown, & Adler, 1991; Meaney, 2001). Preclinical experiments demonstrated that female pups’ experiences during prenatal and pre- weaning periods could significantly affect their future maternal behavior toward their own offspring (Fleming, O’Day, & Kraemer, 1999). Meaney and colleagues (Francis, Diorio, Liu, & Meaney, 1999; Meaney, 2001) repeatedly showed that a trans-generational rule of ‘‘like mother–like daughter’’ exists. They (Francis et al., 1999; Meaney, 2001) found that female pups of rat mothers that received increased maternal care were also ‘‘better mothers’’ in their adulthood than female rats from mothers exhibiting neglected maternal behavior. Thus, it seems Received 1 June 2006; Accepted 5 November 2006 Correspondence to: Romana S ˇ lamberova ´ Contract grant sponsor: Internal Grant Agency of the Ministry of Health of the Czech Republic Contract grant number: 1A8610-5/2005 Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.20203 ß 2007 Wiley Periodicals, Inc.