aim of this research is to determine the way in which cocaine and morphine produce liver damage. The metabolism of cocaine will be studied in mice in order to establish the mature of the active metabolite that is responsible for liver damage. Dye uptake studies will be used to measure changes in liver function. Isolated livers will be employed to examine the effects of cocaine on perfusion and bile secretion. The mobilization of calcium in isolated hepatocytes will be measured fluorometrically. Changes in blood levels of catecholamines and serotonin will be assayed at various time after cocaine and morphine. Adrenergic and serotonergic agonists and antagonists will be used to modify the extent of liver damage after cocaine and narcotic drugs. Nuclear magnetic resonance spectroscopy will be applied to follow the metabolism of cocaine analogues in perfused livers, as well as to reveal early changes in energy metabolism. The results of these experiments should provide new information about effects of cocaine on liver function and circulating neurohormone levels. They should also provide a basis for understanding the nature of the liver damage that is encountered in some human addicts.
