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Newborns delivered to cocaine-abusing mothers are often exposed to other concurrently consumed illicit drugs, which may alter the hemodynamic and cerebral response to cocaine. This study examined the interaction of ethanol, morphine or barbiturate with cocaine on mean arterial pressure (MAP), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in newborn pigs. CBF, CMRO2 and cerebral O2 extraction (CEO2) were measured before and 4 and 10 min after cocaine (1.5 mg/kg i.v.) was administered in piglets that were awake, or pretreated with morphine, ethanol or pentobarbital. In awake piglets, cocaine increased CMRO2 and CEO2 while it had no significant effect on CBF. Conversely, in morphine- and ethanol-pretreated piglets, cocaine decreased CMRO2, decreased CBF and had not effect on CEO2. In awake piglets, cocaine increased MAP, whereas in morphine- or ethanol-pretreated piglets, cocaine decreased MAP. In the pentobarbital group, cocaine had no effect. These data demonstrate that other drugs of abuse alter the hemodynamic and cerebral effects of cocaine in the immature animal and may contribute to the central nervous system abnormalities in 'crack babies'.

The present study investigated the effect of cocaine (COC) on cerebral circulation (CBF) and oxidative metabolism (CMRO2) in the newborn piglet and aimed to relate pharmacokinetics of cocaine to cerebrovascular effects. COC decreased CBF and CMRO2 from 75 to 64 and 4.27 to 3.91 ml/min/100 g, respectively, at 4 min with reduced flow to all brain regions (p < 0.05) which returned to baseline by 10 min. COC was rapidly metabolized with a t1/2 of 43 min and peak plasma concentration of 1,172 ng/ml. Norcocaine (NOR) appeared in plasma and CSF within 3 min of cocaine administration and remained elevated for the duration of the study along with COC in the CSF. These data show that the timing of the peak plasma COC level is associated with maximal decreased CBF. Further, the stable elevated level of COC and NOR in the CSF suggests that biotransformation does not occur in the brain. As a result, accumulation of these drugs may occur in the brain with successive COC use and affect the developing CNS in a deleterious manner.

The effect of prenatal cocaine on acoustic sensorineural reactivity was assessed using reflex modification procedures in infants born to mothers with cocaine abuse (C-exposed). Reflex modification was tested using a controlled eyeblink-eliciting tap to the glabella presented either alone or with a 90-dB SPL tone. The results from 19 C-exposed infants were compared to 19 healthy matched drug-free infants. ANOVA comparison of the two groups showed C-exposed infants were more reactive in general, as indicated by a larger glabellar reflex, and more responsive to auditory stimuli, as indicated by an increased blink when the tone accompanied the tap (p less than 0.05). These data suggest that in utero cocaine exposure may have a direct effect on sensorineural processing and may place these infants at risk for cognitive and/or neurological sequelae.