Triazolam and zolpidem: effects on human memory and attentional processes

Rationale: The imidazopyridine hypnotic zolpidem may produce less memory an d cognitive impairment than classic benzodiazepines, due to its relatively low binding affinity for the benzodiazepine receptor subtypes found in area s of the brain which an involved in learning: and memory. Objectives: The s tudy was designed to compare the acute effects of single oral doses of zolp idem (5, 10, 20 mg/70 kg) and the benzodiazepine hypnotic triazolam (0.125, 0.25, and 0.5 mg/70 kg) on specific memory and attentional processes. Meth ods: Drug effects on memory for target (i.e., focal) information and contex tual information (i.e., peripheral details surrounding a target stimulus pr esentation) were evaluated using a source monitoring paradigm, and drug eff ects on selective attention mechanisms were evaluated using a negative prim ing paradigm, in 18 healthy volunteers in a double-blind. placebo-controlle d. crossover design. Results: Triazolam and zolpidem produced strikingly si milar dose-related effects on memory for target information. Both triazolam and zolpidem impaired subjects' ability to remember whether a word stimulu s had been presented to them on the computer screen or whether they had bee n asked to generate the stimulus based on an antonym cue (memory for the or igin of a stimulus, which is one type of contextual information). The resul ts suggested that triazolam, but not zolpidem, impaired memory for the scre en location of picture stimuli (spatial contextual information). Although b oth triazolam and zolpidem increased overall reaction time in the negative priming task, only triazolam increased the magnitude of negative priming re lative to placebo. Conclusions: The observed differences between triazolam and zolpidem have implications for the cognitive and pharmacological mechan isms underlying drug-induced deficits in specific memory and attentional pr ocesses, as well for the cognitive and brain mechanisms underlying these pr ocesses.