Genetic determinants of sensitivity to pentobarbital in inbred mice

Rationale: We postulated that genetic determinants of different responses to pentobarbital (PB) in mice would differ from response to response. Objectives: Mice from 14 standard inbred strains were tested for sensitivity to several effects of acute PB. Methods: Strains were tested for sensitivity to PB-induced low-dose stimulation and high-dose depression of locomotor activity, reduced rearing, hypothermia, and ataxia assessed on a rotarod, using four doses of PB or saline. Results: Strains differed in sensitivity to PB for all responses. Correlations among strain means indicated that strain sensitivity to a particular effect of PB generalized rather well across doses. Sensitivities to some of the different behavioral responses were also significantly correlated. For example, strains less sensitive to PB-induced enhanced locomotor activity were also significantly more sensitive to the drug's hypothermic effects. Some responses were genetically independent. Brain PB concentrations were also determined, and appeared to be unrelated to inbred strain drug sensitivities. Conclusions: Overall, these results suggest that there are multiple genetic determinants of behavioral sensitivity to PB effects. That is, genetically influenced sensitivity to PB is not. monolithic, but is somewhat specific to the particular response variable studied, a result that also characterizes genetic control of responses to other drugs.