Midazolam does not inhibit association formation, just its storage and strengthening

Abstract

Rationale-Although there have been many studies examining the effects of benzodiazepines on memory performance, their effects on working memory are equivocal and little is known about whether they affect the efficacy of practice of already learned material.Objectives-The objectives in two experiments were to examine (a) whether midazolam impairs performance on a working memory task designed to minimize mnemonic strategies such as rehearsal or chunking of information to be recalled and (b) the effect of midazolam on repeated practice of paired associates that were learned before drug administration.Materials and methods-Both experiments involved subcutaneous administration of 0.03 mg/ kg of body weight of saline or midazolam in within-subject, placebo-controlled designs, involving 23 subjects in (a) and 31 in (b).Results-The drug had no effect on the ability to recall the digits in serial order even though the encoding task prevented the digits from being rehearsed or maintained in an articulatory buffer. Paired associates that were learned before the injection showed a benefit of subsequent practice under saline but not under midazolam. Conclusions-The results suggest that (a) midazolam does not affect the formation of new associations in short-term memory (STM) provided that the presentation rate is not too fast to form these associations when sedated, despite the evidence that the drug blocks long-term memory (LTM) retention of associations; and (b) the potential for over-learning with practice of learned associations in LTM is adversely affected by midazolam such that repeated exposures do not strengthen new learning. KeywordsBenzodiazepine; Working memory; Memory; Binding; Paired associate learning; Practice; MODS task; Midazolam; Over-learning; Digit span Researchers concerned with understanding human memory have sometimes relied on studies of patients with anterograde amnesia to provide insights and constraints on theories of memory mechanisms (Milner 2005). Although this research on patients with amnesia can use accidents

Children's post‐traumatic stress and the role of memory following admission to intensive care: A review

“…The mechanism underlying propofol‐induced amnesia is not well understood, but it appears that information may be acquired but forgotten over time (Veselis, 2006). Benzodiazepines are well known to have an amnesic effect (Kain et al., 2000; Twersky, Hartung, Berger, McClain, & Beaton, 1993), and again, long‐term storage of information appears to be affected, rather than acquisition or formation of associations (Reder et al., 2006). There is also some evidence to suggest that, consistent with adults, implicit learning takes place even though children's explicit recall is severely impaired (Pringle, Dahlquist, & Eskenazi, 2003; Stewart, Buffett‐Jerrott, Finley, Wright, & Valois Gomez, 2006).…”

Effects of lorazepam on visual perceptual abilities

“…The specific WM effects of BZs have so far not received much empirical investigation and results are inconclusive (see Reder et al, 2006). BZs in general are thought to decrease the speed at which information is processed in WM, but not to alter response accuracy (Curran, 2000).…”

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia

“…One alternative explanation for the effect of midazolam on memory is that the memory failures reflect an impairment of consolidation of newly formed associations in long-term memory rather than their formation per se , ( c.f., Reder et al, 2006b; Curtis et al, 2003). This interpretation seems unlikely because retrieval of associations formed just prior to the midazolam injection were unaffected by the drug.…”