PRELIMINARY EVIDENCE FOR METHAMPHETAMINE-INDUCED BEHAVIORAL AND OCULAR EFFECTS IN RAT OFFSPRING FOLLOWING EXPOSURE DURING EARLY ORGANOGENESIS

Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,1)-methamphetamine (MA) HCI (expressed as free base, N = 15) or distilled water (N = 6) by SC injection x 2/day in a 3 ml/kg volume on embryonic (E) days 7-12. Control rats were pair-fed to MA-exposed dams on days E7-18. No control dams failed to deliver; however, of 15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed litters). One additional MA litter had all the offspring die shortly after birth. There was no difference between groups on offspring postnatal (P) body weight. The offspring exposed prenatally to MA had significantly lower olfactory orientation scores (P9, 11, 13) to their home cage scent. In a test of early activity (P10, 12, 14) the MA-exposed progeny were marginally less active than controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened response latency on a test of acoustic startle (P27). Motor activity showed no differential response in MA treated or control offspring to MA (P63) or fluoxetine challenge (P70). However, the MA offspring were more active than controls with respect to central and side activity during the second week of testing. No group differences were found for performance in a straight swimming channel or on the number of errors committed or latency to escape in a complex (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny. However, MA did not effect hippocampal or neostriatal monoamine levels when measured on P28. These data support the hypothesis that MA is behaviorally and ocularly teratogenic to the developing rat and results in functional deficits when compared to offspring of pair-fed controls.