Righting reflex loss studies

In animal studies acetone has been found to potentiate the toxicity of other solvents by altering their metabolism through induction of microsomal enzymes, particularly cytochrome P-450. Reported effects include enhancement of the ethanol-induced loss of righting reflex in mice by reduction of the elimination rate of ethanol increased hepatotoxicity of compounds such as carbon tetrachloride and trichloroethylene in the rat potentiation of acrylonitrile toxicity by altering the rate at which it is metabolized to cyanide and potentiation of the neurotoxicity of -hexane by altering the toxicokinetics of its 2,4-hexane-dione metabolite.Because occupationally exposed workers are most often exposed to a mixmre of solvents, use of the rule of additivity may underestimate the effect of combined exposures. ... 

Studies in mice have shown that MIBK can enhance the ethanol-induced loss of righting reflex by reducing the elimination rate of ethanol. Human response to ethanol may be affected by MIBK, and simultaneous exposure to alcoholic beverages and MIBK should be avoided. 

The role of the a -AR in sedation was revealed in rotarod latency studies, an experimental paradigm that measures the ability of mice to remain on a rotating bar over time impaired motor skills caused by sedation would be predicted to decrease rotarod latency and thus can be interpreted as a measure of the sedative response when unperturbed locomotor response has been documented independently in non-sedated animals. Dexmedetomidine dose-dependently reduced the ability of wild-type mice to remain on the rotarod, whereas a2A-ARl)79N/D79N and ot2A-AR /- mice were resistant to even supramaximal doses (5,29). Consistent with these observations, ot -AR mice did not sleep, as assessed via loss-of-righting reflex (5). These findings indicate that the cx -AR subtype is required to mediate the sedative effects of a2-AR agonists (Table 1). 

---