Effect of aging on anticonflict and CNS depressant activity of diazepam in rats.

Male Fischer 344 rats were examined for an age-dependent sensitivity to the anticonflict and central nervous system (CNS) depressant effects of diazepam. A conflict paradigm was used to measure the ability of single intravenous injections of diazepam to attenuate punishment-induced suppression of behavior and to elicit CNS depression in young, mature, and senescent rats. Senescent rats had the lowest behaviorally active threshold dose. However, diazepam at the behaviorally active threshold dose produced a simultaneous increase in punished and unpunished responding in all three age groups. Punished responding was increased more and over a wider dose range in the young and mature rats than in the senescent rats. Sensitivity to the CNS depressant effects of diazepam was over four times greater in the senescent rats than in the other two age groups. In summary, the results indicate that the behavioral effects of diazepam vary with dosage and age of the rat. The male Fischer 344 rat may be a useful animal model for exploring how diazepam elicits age-related behavioral effects in humans.