Long-lasting microencephaly following exposure to cocaine during the brain growth spurt in the rat

In utero exposure to cocaine has been shown to produce somatic and behavioral effects. As microencephaly is often present in children born from cocaine-addicted mothers, aim of the present study was to develop an animal model for cocaine-induced microencephaly. Rats were treated with cocaine (20, 30 or 50 mg/kg/day, s.c., each dose divided in two equal doses given 3 h apart) from postnatal day 4 through 10. None of the doses had any effect on growth, however, at 50 mg/kg, cocaine caused a significant decrease in brain weight, measured on day 12. The effect of cocaine was similar in male and female rats, and microencephaly was still present in 45-day-old animals. When the same dose of cocaine was given as a single daily injection, long-lasting microencephaly was also present, but it was accompanied by a decrease in body weight and significant toxicity. Ethanol (4 g/kg), used as a positive control, also caused microencephaly without affecting body weight, but, differently from cocaine, its effect was more pronounced in female animals. Blood and brain levels of cocaine and its metabolites norcocaine and benzoylecgonine were measured by HPLC during treatment (postnatal day 8). After administration of the 50 mg/kg dose, concentrations of cocaine were 1.92 micrograms/g in brain and 0.94 microgram/ml in blood. These levels are encountered in cases of cocaine overdoses and have been found in meconium of newborns from crack-addicted mothers.(ABSTRACT TRUNCATED AT 250 WORDS)