Preclinical evaluation of behavioral deficits following hypnotic drug treatment

Most hypnotic medications result in performance decrements, or "hangover effects," the morning after bedtime ingestion. However, the severity of hangover effects with new compounds is difficult to predict prior to clinical trials. This paper describes a preclinical procedure that is predictive of human hangover effects following bedtime ingestion of hypnotic medication. Four cebus monkeys were shaped to discriminate between two levers such that rapid responses following the cue light maximized the probability of reinforcement. Subsequently, performance was evaluated one hr (immediate condition) and 8 3/4 hr (delayed condition) after the administration of flurazepam, triazolam, pentobarbital and placebo. All drugs caused dose-dependent performance decrements in both conditions. Significantly higher doses of triazolam were required to impair performance during the delayed condition as compared to the immediate condition, but no such differences occurred with either flurazepam or pentobarbital. These findings parallel human data which indicate that sleep-inducing doses of flurazepam and many barbiturates, but not triazolam, cause performance decrements the morning after bedtime ingestion.