COCAINE AND COCAINE METABOLITE RESPONSES IN NEWBORN GUINEA PIG CEREBRAL ARTERIES. 457:

Prenatal cocaine exposure in the human fetus is associated with neurologic and developmental morbidity. These sequelae may be related, in part, to the effect of cocaine on cerebral vascular tone and reactivity. Following maternal cocaine administration, cocaine pharmacodynamics in fetal guinea pigs, including placental transfer and cocaine and metabolite concentrations, closely resemble those in humans. Guinea pigs, therefore, are an excellent model for investigating the perinatal effects of cocaine. However, the acute cerebral vascular effects of cocaine in this model are unknown. Using video microscopy of cannulated, pressurized newborn guinea pig cerebral arteries(baseline diameter 280±35μm at 3-14days), we studied the acute effects of cocaine and its major metabolites on cerebral vascular tone. Transluminal pressure was maintained at 10mmHg; in vitro segment length approximated in vivo length. Cocaine and several metabolites elicited dose-dependent constriction (figure): cocaine> benzoylecgonine > cocaethylene > > norcocaine > ecgonine methyl ester. Cocaine-elicited vasoconstriction was attenuated by phentolamine, an α-adrenergic receptor antagonist. Newborn guinea pig cerebral arteries demonstrate significant vasoconstriction to cocaine and its metabolites, thus providing an ideal model to further study the cerebral vascular sequelae of prenatal cocaine exposure. Supported by NIH DA07607.