Abstract 401 Poster Session III, Monday, 5/3 (poster 164)

The long-term effects of prenatal cocaine exposure on brain development are unknown. To assess the persistent neurotoxic effects of in utero cocaine exposure, pregnant rats were administered saline or cocaine (20 mg/kg cocaine, sc, bid) from day five of gestation until parturition. Brains of adult (120 d) offspring were analyzed by proton magnetic resonance spectroscopy (1H-MRS). Several functional markers were measured, including N-acetyl aspartate (NAA), [a marker of neuronal integrity], creatine (a marker for energy metabolism), and gamma-amino butyric acid (GABA), [a marker for neurotransmission]. Relative to control animals, offspring exposed to cocaine in utero had significant (p<0.05) reductions of NAA (13% for males and females) and creatine (16 vs. 18%, female vs. male, respectively) in the left frontal cortex. NAA levels were also decreased (19 vs. 11%; female vs. male, respectively) in the left striatum. GABA was reduced in the left frontal cortex (18%) and left hippocampus (16%) in male offspring only. We conclude that offspring exposed to cocaine in utero exhibit significant long-term changes in brain metabolites in a sex- and brain region- specific manner. Because 1H-MRS can be performed on the human brain in vivo, results from this study can be related to studies of humans exposed to cocaine and other drugs of abuse during early development.

Funded by NIH Grant 3-M01-RR00425-2754