Effects of aging on ethyl alcohol (EtOH) pharmacodynamics were examined over progressive dosing schedules (0.4, 0.6, 0.8, 1.0 g/kg) in groups of young (25.0 +/- 2.9 years), middle-aged (41.1 +/- 6.6 years), and young-elderly adults (60.9 +/- 2.6 years) using three computerized cognitive-neuromotor tasks: digit-symbol substitution (DSS), keypad reaction time (KRT), and subcritical tracking (SCT). Hysteresis curves of performance impairment (adjusted for pre-drug baseline) as a function of blood alcohol concentration (BAC) were examined for time-course effects, and regression analyses were performed to assess the contribution of age beyond that accounted for by BAC. Results reflected differences in the patterning but not magnitude of impairment for elderly subjects, with earlier decrements and more rapid acute tolerance observed for DSS, in conjunction with less pharmacodynamic sensitivity for SCT. Regression analyses furthermore indicated that age and impairment were negatively related, arguing against synergistic intoxication effects as a function of aging. Analyses specifically comparing performance at baseline versus legally intoxicating BACs (> 1.0 mg/ml) likewise reflected a lack of interactive effects involving the elderly. Elderly subjects nevertheless exhibited significantly lower baseline performance for DSS and KRT than young subjects and achieved higher BACs with equivalent doses. These latter findings support the exercise of caution by elderly individuals consuming EtOH prior to engaging in neuromotor pursuits such as driving.

Eight healthy young males were administered single doses of lorazepam (4 mg), clonazepam (4 mg), alprazolam (2 mg) or placebo, and their performance on behavioral tasks was monitored for 7 h. Lorazepam and clonazepam impaired performance on subcritical tracking, a primarily neuromotor task, for 2-4 h longer than alprazolam. Although the duration of impairment of the digit symbol substitution task was less discrepant for the three drugs, clonazepam and lorazepam still affected performance for a longer period of time than alprazolam. The rapid development of acute tolerance was indicated by clockwise hysteresis curves for all the drugs on the SCT task and for clonazepam and alprazolam on the DSS task. The maximum effect, effect offset rate and duration of the drug effect are discussed in relation to molecular structure and receptor affinity.