The aim of the present study was to compare the response to sub-chronic application of methamphetamine (MA) in adulthood in male and female rats prenatally exposed to the same drug. The spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to 5mg/kg MA or saline (SAL) were tested in a Laboras apparatus (Metris B.V., Netherlands) for five consecutive days, 1hr daily. MA 1mg/kg or SAL were used as a challenge prior to testing. Our results showed that rats prenatally exposed to MA were more sensitive to sub-chronic administration of MA in adulthood than prenatally SAL-exposed rats. However, this sensitizing effect of prenatal MA exposure was manifested differently in males and females. In contrast, prenatal MA exposure decreased baseline locomotion in females. This study indicates that gender plays an important role in the sensitivity to MA during prenatal development and in adulthood. (c) 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 232242, 2013