Life sciences
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To assess whether the anesthetic and anticonvulsant activities of alphaxalone display diurnal variability, groups of Syrian hamsters were studied at 4 h-intervals during a 24 h-cycle. The administration of alphaxalone (5 mg/kg) brought about a greater anesthetic activity (loss of righting reflex) at the middle of the photophase. When assessed in hamsters injected with 3-mercaptopropionic acid, alphaxalone displayed maximal anticonvulsant activity at the 4th of darkness. Evaluation of the time needed for first convulsive response indicated that alphaxalone did not show time-dependent effects, while in control hamsters seizure threshold was low during daylight and attained maximal values at night, showing a peak in seizure threshold at light-dark transition.
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Comparative Study
Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene).
The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomotor stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. ⋯ In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.
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Behavioral responses to stressors and the effects of stressors on maternal behavior change with mothering experience. Corticotropin-releasing hormone (CRH) is released by stressors and produces stress-like behavioral effects. We tested the effects of ICV infusion of ovine CRH (0.5-4 ug) on pup-directed behaviors in ovariectomized, ovarian steroid-treated virgin rats that were either naive to pups or that had three days of mothering experience. ⋯ The magnitude and duration of inhibition, especially at the 1 ug dose, were less in rats with mothering experience. Higher doses of CRH (1 - 4 ug) significantly increased pup-killing in rats that were naive to pups. In contrast, CRH produced no pup-killing in rats with mothering experience.
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The changes in hepatic energy state were assessed by 31P-nuclear magnetic resonance spectroscopy (31P-MRS) and arterial ketone body ratio (AKBR) in brain dead dogs. 31P-MRS and AKBR were measured before and at 3 hours after brain death. Wiggers' shock model was employed to compare the energy metabolism during hypotension. 1) The brain death model: Systemic blood pressure changed from 178.3/115.0 mmHg (mean) in the control period, to 259.5/162.5 mmHg during Cushing phenomenon (CU period) and to 63.3/51.7 mmHg after completion of brain death (BD period). beta-ATP/Pi increased from 1.27 +/- 0.14 (mean +/- SEM) to 1.46 +/- 0.16 in the early CU period, and then decreased to 1.11 +/- 0.15 at 60 minutes after BD, followed by a gradual increase to 1.33 +/- 0.13 at 3 hours after BD. Intracellular pH (pHi) increased alkaline to the control value. ⋯ AKBR decreased from 1.00 +/- 0.11 to 0.21 +/- 0.04 in the EX period and increased to 1.08 +/- 0.12 in the RT period. The energy metabolism of the liver was well maintained in the state of brain death in spite of remarkable hypotension, although that was not the case with Wiggers' shock model. It was suggested that the combination of 31P-MRS and AKBR was useful for the evaluation of graft liver viability.
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The effects of L-buthionine sulfoximine (L-BSO), 2-cyclohexene-1-one and diethylmaleate (DEM) on the concentration of rat brain glutathione (GSH) were investigated. Both DEM and 2-cyclohexene-1-one, administered subcutaneously, produced marked and rapid reduction of brain GSH, but 2-cyclohexene-1-one appeared less toxic than DEM. Six hours after 2-cyclohexene-1-one (100 microliters/kg) the striatal GSH concentration was 35% of control values, whereas the level was 55% of controls at 24 h and 80% of controls at 48 h. ⋯ The disappearance rate of GSH after L-BSO alone gives an estimate of the turn-over of GSH. We found the turn-over of GSH to be higher in the substantia nigra pars compacta than in the striatum. The present work suggest that L-BSO and 2-cyclohexene-1-one would be very useful for evaluation of the biological role of GSH in the central nervous system.