Trichloroethylene (TCE) was metabolized by cytochrome P-450 containing mixed-function oxidase systems to chloral (2,2,2,-trichloroacetaldehyde), glyoxylic acid, formic acid, CO, and TCE oxide. TCE oxide was synthesized, and its breakdown products were analyzed. Under acidic aqueous conditions the primary products were glyoxylic acid and dichloracetic acid. The primary compounds formed under neutral or basic aqueous conditions were formic acid and CO. TCE oxide did not form chloral in any of these or other aqueous systems, even when iron salts, ferriprotoporphyrin IX, or purified cytochrome P-450 was present. Ferric iron salts catalyzed the rearrangement of TCE oxide to chloral only in CH2Cl2 or CH3CN. A 500-fold excess of iron was required for complete conversion. A kinetic model involving the zero-order oxidation of TCE to TCE oxide by cytochrome P-450 and the first-order degradation of the epoxide was used to test the hypothesis that TCE oxide is an obligate intermediate in the conversion of TCE to other metabolites. Kinetic constants fo the breakdown of TCE oxide and for the oxidative metabolism of TCE to stable metabolites were used to predict epoxide concentrations required to support the obligate intermediacy of TCE oxide. The maximum levels of TCE oxide detected in systems using microsomal fractions and purified cytochrome P-450 were 5-28-fold lower than those predicted from the model. The kinetic data and the discrepancies between the observed metabolites and TCE oxide breakdown products support the view that the epoxide is not an obligate intermediate in the formation of chloral, and an alternative model is presented in which chlorine migration occurs in an oxygenated TCE-cytochrome P-450 transition state.
3 rhesus monkeys were obtained from the Regional Primate Center, University of Wisconsin. These animals had been subjected to total social isolation during their 1st yr. of life. 3 feral monkeys of the same age constituted the normal group. The animals were trained to perform an instrumental avoidance response to a visual stimulus. There were no differences in acquisition of the response either in terms of instrumental behavior or conditioned cardiac responses. The animals were then paired in all possible combinations for communication of affects tests using the cooperative-avoidance technique. The monkey which received the conditioned stimulus was visible to the animal having access to the response bar via closed-circuit television. The results, both instrumental and physiological, indicated that isolate monkeys were incapable of utilizing facial expressions of other monkeys in order to perform appropriate avoidance responses. The isolates also were found to be defective senders of facial expression.
The various changes in mood and behavior that may occur in patients treated with adrenocorticotrophic hormone (1,6) have made it pertinent to assess the effect of exogenous ACTH on behavior motivated by noxious stimulation. That some effect of ACTH on avoidance conditioning does occur is revealed in studies discussed by Mirsky, Miller, and Stein (5).In avoidance conditioning the animal must respond appropriately to the conditioned stimulus in order to prevent the occurrence of the painful unconditioned stimulus. Consequently, it may be postulated that any modification of the response to a noxious stimulus would be reflected in avoidance conditioning.
METHOD
SubjectsThirty-one male Wistar rats 100 to 120 days old were used. The Ss were maintained on an ad libitum supply of food and water throughout the experiment. The animals were randomly assigned to the experimental conditions.
A pparatusThe tests were conducted in a two-compartment apparatus. The unit was 23 in. long, 7 in. wide, and 9 in. high. A 2-in. barrier of stainless steel liars % in. in diameter, l^ in. apart, separated the two compartments. The top bar of the barrier was mounted on bearings to prevent perching. The floor was a grid of stainless steel rods identical in size and spacing to those described for the barrier. The two ends and the top were made of wood, and painted while inside. One side consisted of a sheet of white milk glass. Illumination was provided by two 25-w. bulbs located behind this translucent glass. The remaining side consisted of two pieces of plain glass with a black cloth inserted between them. This made it possible to observe the animal without the distraction of movements by E.A push-button switch activated a buzzer and a timedelay relay that automatically delivered a shock to the animal after S sec. if it failed to respond (110 v. with 85,000 ohms in series with the animal). Another push-
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