Alcohol-induced inhibition of cocaine metabolism and the formation of cocaethylene in neonatal rats.

Due to the significant species differences in the timing of different stages of brain development, to study the effects of drugs during the period equivalent to the third trimester in humans it is necessary to administer the drugs to neonatal rats. rather than in utero. In this study, we investigated the pharmacokinetic interactions between alcohol and cocaine. Such information is critical in understanding the roles of alcohol and cocaine in mediating neuroteratogenesis. Sprague-Dawley rat pups (10 days old) were given IP injections of alcohol (3.3 or 5.0 g/kg) and/or cocaine (40 mg/kg). At 20, 60, or 100 min (60 and 100 min for 3.3 g/kg alcohol only) after injections, 20 microl of tail blood was collected for blood alcohol concentration (BAC) determination. Immediately after tail blood collection, blood was collected and pooled for determinations of blood cocaine (BCC), benzoylecgonine (BBC), and cocaethylene concentration (BCEC). The slopes of the ascending BAC curves were unaffected in the presence of cocaine. BCC levels declined significantly as a function of time after the peak level at 20 min postinjection time. BCC levels were unchanged in pups receiving 3.3 g/kg alcohol, but the levels were significantly higher in 5.0 g/kg pups 20 min after injections. BBC concentrations were reduced to nearly 50% in the presence of alcohol (both doses) 20 min after injections. BCEC was detected at all time points when both alcohol and cocaine were injected. Taken together, these findings indicated that the enzymatic systems involved in converting cocaine to cocaethylene were functional at an early postnatal age, and the metabolism of cocaine was affected by the presence of alcohol in neonatal rats.