Money as a tool to extinguish conditioned responses to cocaine in addicts.

Classical conditioning principles offer a nondrug way to treat cocaine dependence. Eleven male subjects with the primary diagnosis of cocaine dependence were placed into one of two groups. The experimental group was asked to handle $500 cash in a mock budgetary task. The control group was asked to just imagine handling and budgeting the money. The subjects rated their craving-related feelings before and after each task. The experimental group showed significantly more craving after the money-handling task as compared to the control group, and the scores improved with time and as more tasks were completed. These data show that craving induced by handling cash is powerful and can be attenuated, at least on a short-term basis, using classical extinction procedures.

Possible mechanism for late gestational development of the antioxidant enzymes in the fetal rat lung.

We hypothesized that a possible mechanism to explain the significant increases that occur in the pulmonary antioxidant enzyme (AOE) system late in gestation might be an endogenous increase in the normal reactive O2 substrates for these enzymes. We found that lung O2 free radical formation increased approximately 175% between fetal day 18 and birth (p < 0.01). We also found that late fetal rat lung mitochondrial and microsomal rates of AOE substrate (H2O2) generation increased markedly, and there was also significantly increased lung lipid peroxidation products with increasing gestational age. These definite elevations in reactive O2 species production in parallel with the time course of maturational elevations in the pulmonary AOE system, suggest that increasing enzyme substrate concentrations could be a primary controlling mechanism for increasing lung AOE gene expression in preparation for birth of the newborn.

Failure of premature rabbits to increase lung antioxidant enzyme activities after hyperoxic exposure: antioxidant enzyme gene expression and pharmacologic intervention with endotoxin and dexamethasone.

Premature rabbits, unlike full-term rabbits, are unable to mount a protective increase in pulmonary antioxidant enzyme (AOE) activities in response to 48 h of hyperoxic exposure and demonstrate increased pulmonary O2 toxicity compared with full-term rabbits. To examine AOE gene expression of CuZn superoxide dismutase (SOD), Mn SOD, catalase, and glutathione peroxidase in preterm versus term rabbits in response to hyperoxia, 29.5 d preterm rabbits (delivered by hysterotomy) and term rabbits (spontaneously vaginally delivered) were exposed to 48 h of > 90% O2 or room air. Preterm rabbits had a significant increase in CuZn SOD mRNA without corresponding AOE activity increases, suggesting translational/posttranslational inhibition. In full-term rabbits, the magnitude of lung AOE mRNA changes was associated with concordant magnitude changes in activities of CuZn SOD, Mn SOD, and catalase, suggesting pretranslational regulation of AOE gene expression; glutathione peroxidase, however, appears to be regulated translationally/posttranslationally. To investigate potential pharmacologic means of overcoming the susceptibility of the preterm rabbit to O2 toxicity, 29.5 d preterm rabbits received 20-40 micrograms/kg of Salmonella typhimurium endotoxin or diluent S.C. (after birth and at 24 h); in separate experiments, pregnant rabbits received intramuscular injections of dexamethasone (0.01-0.05 mg/kg) or saline on gestational d 27.5 and 28.5 and underwent hysterotomy at 29.5 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor increases antioxidant enzyme and surfactant system development during hyperoxia and protects fetal rat lungs in vitro from hyperoxic toxicity.

Epidermal growth factor (EGF) has been shown to accelerate fetal lung maturation in rabbits, lambs, and rhesus monkeys in vivo and increase surfactant synthesis in vitro. Its effect on the maturation of the lung antioxidant enzyme system, however, is unknown. We studied the effect of EGF (10 nM) on 19-d fetal rat lung explant cultures in serum-free medium in air/5% CO2 or > 90% O2/5% CO2 compared with similarly grown control cultures in air or hyperoxia at 72 h. Fetal lung activities of superoxide dismutase and catalase were unchanged by EGF in air, whereas glutathione peroxidase activity was significantly decreased (p < 0.05 versus air control). However, in hyperoxia, EGF-treated fetal lung cultures had significantly elevated superoxide dismutase and catalase activities (p < 0.01) versus O2-exposed controls, and glutathione peroxidase activity similar to that of controls. The mRNA levels for all the antioxidant enzymes showed patterns similar to the enzyme activities except in the case of Cu,Zn-superoxide dismutase mRNA, which increased in EGF-air cultures. EGF decreased the rate of 3H-choline incorporation into disaturated phosphatidylcholine in air (p < 0.01 versus air control), but increased disaturated phosphatidylcholine synthesis in response to hyperoxia (p < 0.01 versus O2 control). The histologic appearance of EGF-treated cultures in O2 was superior to that of O2-exposed controls, which showed thickened septal walls, decreased surfactant in the air spaces, and epithelial cell mitochondrial swelling. EGF therefore accelerates antioxidant enzyme and disaturated phosphatidylcholine maturation under hyperoxic conditions and protects fetal rat lung cultures from hyperoxic injury.(ABSTRACT TRUNCATED AT 250 WORDS)