Aging: Changes in a passive-avoidance response with brain levels of temazepam

Abstract

Acute intravenous (IV) injections of temazepam were examined for the ability to impair the performance of young (3–4-month-old), mature (12–15-month-old) and old (28–30-month-old) male Fischer 344 rats in the step-down task relative to vehicle-injected controls. The effect of temazepam on the passive-avoidance response could be characterized as a U-shaped function of age. The performance of the mature rat was not significantly impaired by an IV injection of temazepam between 18 and 320 μg/kg. Temazepam was more effective in impairing the performance of the young and old rat. The brain levels of temazepam after a single IV injection of 18 μg/kg in mature and senescent rats, and 32 μg/kg in young rats were measured over a 2-hour time period. The brain of the mature rat was exposed to less temazepam between 0 and 120 minutes than the brain of the old rat. Therefore, the increased sensitivity of the senescent rat relative to the mature rat may in part be due to changes in the pharmacokinetics of temazepam. However, the inability of temazepam (between 18 and 320 μg/kg) to impair the performance of mature rats in the passive-avoidance task suggests that pharmacodynamic changes may be involved in the decreased sensitivity of mature rats relative to young and senescent rats.