COCAINE EXPOSURE DURING THE BRAIN GROWTH SPURT FAILED TO PRODUCE CEREBELLAR PURKINJE-CELL LOSS IN RAT PUPS

Previous studies in our laboratory indicated that cocaine exposure dur ing the brain growth spurt period, a developmental stage vulnerable to various teratogens, did not produce microencephaly (gross brain weigh t measures). However, neonatal cocaine exposure has been shown to affe ct motor coordination and balance, which are both sensitive to cerebel lar damage. The purpose of this study was to investigate whether cocai ne exposure during the brain growth spurt period could result in the l oss of cerebellar Purkinje cells, a neuronal population known to be vu lnerable to other teratogenic insults. Sprague-Dawley rat pups were ra ndomly assigned to either cocaine-treated groups (40, 80 mg/kg s.c.) o r a gastrostomy control group, and were reared using an artificial-rea ring method from postnatal days (PDs) 4 through 9. On PD 10, these ani mals were perfused and the cerebella were extracted and processed for cell counts. Estimates of Purkinje cell numbers were obtained using a 3-dimensional optical disector method. The results using this stereolo gical method demonstrated no significant Purkinje cell loss in respons e to cocaine treatment, even at a dose which has been shown to result in high mortality. The failure of cocaine to produce significant Purki nje cell loss (present finding) or microencephaly (previous finding) a dds to the evidence indicating that cocaine is not a potent neuroterat ogen. (C) 1996 Wiley-Liss, Inc.