Michael J. Ulissey

Chronic cocaine administration decreases dopamine synthesis rate and increases [3H] spiroperidol binding in rat brain

Chronic administration of cocaine HCl (10 mg/kg, IP, every 12 hours for 10 consecutive days) resulted in a significantly decreased rate of accumulation of 3,4-dihydroxyphenylalanine following decarboxylase inhibition (-27 to -33%) and of homovanillic acid following probenecid treatment (-25 to -34%) in rat striatum, limbic forebrain and midbrain. In addition, the Bmax for [3H]-spiroperidol receptor binding was significantly increased (+24 to +36%) in these brain regions following chronic cocaine administration. These changes were observed 60 days following termination of the chronic cocaine treatment regimen. These data suggest that cocaine produces long-term, if not permanent, effects on central dopamine synthesis.

Halothane Anesthesia Alters Cerebral Enzymes: A Histochemical Study in the Rat

Cerebral forebrain arterioles and neuropil were analyzed histochemically to determine the effects of halothane anesthesia on key enzymes of aerobic and anaerobic metabolism, as well as the hexose monophosphate shunt in rats. Significant changes were noted in all five enzymes examined in arterioles, while no changes were observed in the two enzymes involved in aerobic metabolism in the neuropil. Our data suggest that surgical anesthetic levels of halothane can impair forebrain metabolism and lead to altered electrophysiological responses.

Low doses of L-tryptophan are lethal in rats with adrenal insufficiency

Adrenalectomy decreased the LD50 value for L-tryptophan from greater than 1000 mg/kg in normal rats to 11.6 mg/kg. The LD50 in adrenalectomized rats was restored to normal by corticosterone replacement therapy. Administration of metyrapone, which blocks the synthesis of adrenal steroids, to normal rats decreased plasma corticosterone levels by approximately 50% and decreased the LD50 from greater than 1000 mg/kg to 24.9 mg/kg. Neurochemical analysis revealed a large increase in tissue tryptamine levels following administration of L-tryptophan in rats with adrenal insufficiency. Therefore, it appears that death due to L-tryptophan in animals with adrenal insufficiency is due to formation of excess tryptamine and, consequently, an elevation in blood pressure and other cardiovascular dysfunctions.

Ethanol Alters Microvasculature Enzymes in the Rat Forebrain

Forebrain arterioles were analyzed histochemically to determine the effects of an acute administration of ethanol on key enzymes of aerobic and anaerobic metabolism as well as on the hexose monophosphate shunt in rats. The enzymes were glucose 6-phosphate dehydrogenase, cytochrome oxidase, lactate dehydrogenase, beta-hydroxybutyrate dehydrogenase, and isocitrate dehydrogenase. All enzymes were quantified under two conditions: 1 h and 2 days after ethanol administration. Significant changes were noted in four of the five enzymes measured after 1 h and in all five enzymes when measured 2 days after ethanol administration. Our data suggest that ethanol may cause impaired metabolism in the forebrain microvasculature, which, in turn, may account for some of the characteristic behavioral effects of acute ethanol administration.

Halothane Depletes Cardiac Microvasculature Enzymes in the Rat

Left ventricular arterioles from Sprague-Dawley rats were analyzed histochemically to determine the effects of halothane administration on key enzymes of aerobic and anaerobic metabolism, as well as on key enzymes of the hexose monophosphate shunt. Significant decreases occurred in cytochrome oxidase (-42%) and beta-hydroxybutyrate dehydrogenase (-57%). No significant changes were observed in isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, or lactate dehydrogenase. These data suggest that anesthetic levels of halothane can cause impaired metabolism in the coronary microvasculature.

Chloral Hydrate Anesthesia Alters Cerebral Enzymes in the Rat

Cerebral forebrain arterioles and neuropil were analyzed histochemically to determine the effects of chloral hydrate anesthesia on key enzymes of aerobic and anaerobic metabolism, as well as the hexose monophosphate shunt in rats. Significant decreases were observed in cytochrome oxidase, and beta-hydroxybutyrate dehydrogenase in arterioles, while glucose-6-phosphate dehydrogenase and isocitric dehydrogenase showed a significant increase and lactate dehydrogenase showed no significant change. In the neuropil, cytochrome oxidase, isocitrate dehydrogenase and glucose-6-phosphate dehydrogenase showed significant increases following chloral hydrate administration, while beta-hydroxybutyrate dehydrogenase and lactate dehydrogenase showed no significant changes. These data suggest that surgical anesthetic levels of chloral hydrate can impair forebrain metabolism which may lead to altered electrophysiological responses.

Acute Administration of Chloral Hydrate Depletes Cardiac Enzymes in the Rat

The arterioles of the left cardiac ventricle were analyzed histochemically to determine the effects of an acute administration of chloral hydrate on key enzymes of aerobic and anaerobic metabolism, as well as the hexosemonophosphate shunt in rats. Significant changes were noted in three of the 5 enzymes examined. Our data suggest that nontoxic levels of chloral hydrate can cause impaired coronary metabolism.