State‐dependent retrieval and midazolam

Abstract

This experiment investigated the phenomenon of state-dependent retrieval with midazolam by comparing performance after midazolam + placebo with that after reversal with the benzodiazepine antagonist flumazenil, in tests of explicit and semantic memory and judgements of remncy. The subjects completed analogue rating scales and psychomotor tests to provide measures of sedation. Midazolam (0.05 mg/kg) impaired recall and recognition of pictures and performance in the digit-symbol substitution task. There were no significant statedependent effects with this dose. Midazolam (0.075 mg/kg) impaired recall and recognition of words and pictures and recognition of coloured slides of complex scenes. There were significant statedependent effects on all the recognition tests, i.e. the group tested after reversal with flumazenil (0.5 mg) performed worse than that tested after placebo. Midazolam (0.075 mg/kg) also impaired recency judgements and performance in the number cancellation and digit-symbol substitution tests, but there were no state-dependent effects in these tests. To determine whether subjects had insight into their memory impairments, for each task they were asked to rate on an analogue scale whether they thought their memory would be 'better or worse than usual'. Those tested with midazolam (0-075 mgkg) showed no insight into their memory impairments and there were negative correlations between actual and estimated performance. However those reversed with flumazenil were aware their memory was worse than usual and had positive correlations between actual and estimated performance, similar to those shown by subjects tested undrugged.

Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

“…This means a change from a relatively highly drugged state to a low or non-drugged state or reverse. It has been reported that state change from BZD drug to placebo condition may negatively affect on memory retrieval in comparison to continuous BZD condition [ 54 ].…”

The effect of midazolam on implicit and explicit memory in category exemplar production and category cued recall

“…Such a result would provide evidence that implicit and explicit memory are mediated by different memorial factors. 1 Studies using the benzodiazepine antagonist flumazenil have shown evidence inconsistent with the hypothesis that midazolam amnesia is due to a state-dependent memory effect in free recall (Birch & Curran, 1990;File, Goodall, Mabbutt, Harris, & Skelly, 1993). Specifically, such studies show that although flumazenil reverses midazolam's major sedative effects (e.g., psychomotor performance returns to normal levels), midazolam's amnesic effects remain, and are as strong as in a condition where participants are administered an injection of saline prior to free recall.…”

Effects of Δ9-THC and WIN-55,212-2 on place preference in the water maze in rats

“…Diazepam-induced place preference was not state dependent (Overton 1984) because a spatial bias was measured in the absence (probe trial 1 in experiment 2B) and presence (probe trial 2 in experiment 2B) of the drug. State-dependent alterations in learning are well established for benzodiazepines (File et al 1993). …”