Inhibition of Na+/K+ ATPase by cardiac glycosides has been shown to potentiate toxic effects of excitatory amino acids and mitochondrial poisons in neurons in vitro. The present study tested the hypothesis that the systemic administration of the cardiac glycoside, digoxin, potentiates effects of the dopamine neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) in vivo. Mice were injected with digoxin (1 mg/kg) or vehicle followed by MPTP (20 mg/kg) or saline 1 h later. After 1 or 8 days, mice were euthanized and dopamine levels in the striatum were measured by high-performance liquid chromatography with electrochemical detection. MPTP caused a significant 35-45% reduction in striatal dopamine levels compared to those in control mice. However, pretreatment with digoxin completely prevented the MPTP-induced dopamine depletion. This result was unexpected and suggests that cardiac glycosides may protect against MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMedDate not supplied

Correlation of Purkinje neuron depression and hypnotic effects of ethanol in inbred strains of rats.

The effect of locally applied ethanol on spontaneous discharge rates of cerebellar Purkinje neurons was compared in two inbred strains of rats which differ in their sensitivities to the acute hypnotic effects of this agent. Ethanol, applied locally to neurons by micropressure ejection with multibarrel micropipettes, was significantly more potent for reducing neuronal firing rates in Fischer 344 rats when compared to Brown Norway rats. The hypnotic effect of ethanol, measured by loss of righting reflex, lasted significantly longer in the Fischer 344 strain of rats. These results suggest that susceptibility to a behavioral effect of ethanol might correlate with an effect on firing rates of cerebellar Purkinje cells in rats. In mice, selective breeding has produced "long-sleep" and "short-sleep" strains of mice which differ not only in sensitivity to the hypnotic effect of ethanol, but also to the sensitivity of cerebellar Purkinje cells to depressant effects of this drug. Because electrophysiological investigations are in many ways easier to perform in rats than in mice, genetic differences in rats may provide an important means for analyzing central nervous system actions of acute ethanol administration.

Animals↗

PubMedDate not supplied

Metabolism, tissue distribution, and elimination kinetics of phenytoin in the frog.

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Animals↗