Limited memory impairment after temazepam

In order to examine the effects of temazepam on memory, a battery of cognitive tests and analogue mood ratings were given to healthy volunteers after oral administration of 5, 10 and 30 mg. The lowest dose had no effect and 10 mg only significantly increased self-ratings of well-being. Temazepam (30 mg) significantly improved recall of items learned prior to drug administration, but impaired recall and recognition of word lists acquired after drug administration. However, when retrieval was assessed indirectly using a backwards reading task there was no impairment, indicating that automatic information processing was unaffected. Temazepam (30 mg) significantly reduced self-ratings of anxiety and increased those of sedation. It also significantly impaired performance in symbol copying, digit-symbol substitution and number cancellation tasks. It is striking that, at a dose that was sedative and impaired many aspects of performance, temazepam nonetheless improved retrieval of items learned prior to drug administration. © 1998 John Wiley & Sons, Ltd.     

An investigation of the range of cognitive impairments induced by scopolamine 0·6 mg s.c

The present study was conducted to determine the degree to which impairments in attention accompany the memory deficits produced by scopolamine. Eighteen healthy young volunteers received scopolamine 0·6 mg subcutaneously on three experimental sessions and placebo on three others. On each session, prior to, and 60 min after injection, the subjects underwent an automated computerized battery of 11 cognitive tasks. The study was run double-blind and the order of treatment conditions over successive visits was counterbalanced between subjects. Scopolamine produced marked and significant decrements on all major aspects of performance from the battery. The drug lowered the efficiency of the detection and processing of information in tests of visual vigilance, rapid information processing, choice reaction, letter cancellation and logical reasoning. These effects were accompanied by a lowering of critical flicker-fusion frequency and subjective alertness. Memory was also impaired on tests of immediate recall, delayed recall, recognition and memory scanning. These findings confirm and extend previous work, demonstrating that scopolamine impairs the selection and evaluation of environmental information, as well as reducing the likelihood of information being subsequently recalled or recognized. Whether the former effects contribute to the latter is not known, but this must be considered a possibility. This potential role of processing deficits in memory loss associated with cholinergic blockade is briefly considered in relation to the cholinergic hypothesis of geriatric memory loss.     

Selective effects of triazolam on memory

The effects of a benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious awareness was not altered by triazolam. Similarly, triazolam did not affect subjects' abilities to access semantic memory.     

Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval

RATIONALE: Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities. Acute tryptophan depletion (ATD) in healthy subjects impairs episodic memory, but the mechanism of this is unclear. OBJECTIVES: To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects. METHODS: Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan, in a double blind, crossover design. Event related potentials (ERPs) were recorded during a well-validated episodic memory task performed 5 h after drink ingestion. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study. RESULTS: ATD led to an 84+/-5% reduction in plasma free tryptophan concentrations, and significantly impaired episodic memory recall. ERP recordings demonstrated previously reported left parietal and right frontal "old/new" differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items. ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp, but there was no interaction with item type. Topographical analysis of the old/new difference revealed no significant treatment by site interaction. CONCLUSIONS: ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects. This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and/or consolidation.     

Effects of ethanol and temazepam on episodic and semantic memory: a dose–response comparison

Drug‐induced memory impairment is most apparent for long‐term memory, but it is unclear whether this effect is restricted to episodic memory with no effect on semantic memory. Here we compare how the formation of new semantic and episodic memories are affected by ethanol and temazepam. Eighteen subjects (12 male, 6 female; age 19–43 years; weight 52–104 kg) took part in five sessions in which they received by mouth, in random order: (E2) ethanol, 0.8 g/kg, maximum 60 g males, 50 g females; (E1) ethanol, 75 per cent of the dose for E1; (T2) temazepam 20 mg; (T1) temazepam 15 mg; (P) placebo. They carried out a series of tests including learning of invented ‘facts, a measure of the acquisition of new semantic memory; the Buschke test, a measure of short‐ and long‐term learning of words; Digit–Symbol substitution, a measure of psychomotor speed; and Visual Analogue Scales. Both acquisition of new semantic memory and the long‐term measure from the Buschke were impaired by both drugs. The effects of ethanol were more marked than those of temazepam for the memory tests at the doses used here, particularly for the Buschke. Psychomotor impairment as assessed by Digit–Symbol substitution speed was equally affected by both drugs. Subjects rated themselves more drunk on ethanol than on temazepam, but drowsiness was similar for the two drugs. These results show that both drugs impair the acquisition of new semantic memory as well as new episodic memory, and suggest that it is new long‐term memory formation that is impaired by these drugs and not the formation of a specific type of memory, such as episodic memory. Copyright © 1999 John Wiley & Sons, Ltd.     

Nicotine improves memory for delayed intentions

RATIONALE: The present paper asked first whether the cholinergic agonist nicotine improves memory for delayed intentions (prospective memory, ProM) and second whether pharmacological dissociation would support the psychological distinction that is made between strategic (effortful) and automatic (non-effortful) intention activation in prospective memory. OBJECTIVES: To use nicotine as a pharmacological tool with which to examine the neurochemical bases of prospective memory and to dissociate strategic from automatic components of ProM retrieval. METHODS: In three experiments, minimally deprived (2 h) smokers either smoked or abstained prior to completing a standard prospective memory study. This involved participants in the simultaneous processing of a ProM task and a cover task (ongoing between the setting and the recall of the intention). Here, the ongoing task involved lexical decision (LDT), while the ProM task required a response to pre-specified target items occurring within the LDT stimuli. Variations in task instructions were used to manipulate the processing requirements of the ProM task, the attention allocated to the ProM task and the balance of importance assigned to the ongoing and ProM tasks. RESULTS: In experiment 1, where the ProM processing was automatic, nicotine did not improve ProM accuracy. In experiment 2, where the ProM task involved strategic processing, positive effects of nicotine were observed. In experiment 3, we covaried ProM task instructions, assigned task importance and nicotine conditions. We observed a main effect of nicotine on ProM accuracy, a main effect of task on ProM accuracy and a main effect of assigned task importance on ProM accuracy. There were no interactions between the factors. CONCLUSIONS: Employing both direct and indirect manipulations of strategic engagement, we demonstrated nicotine-induced enhancement of performance on the ProM task. The results are consistent with the view that relatively small changes in instruction and in task variables engage strategic processing in a ProM task and that when these conditions stretch cognitive resources, nicotine may significantly improve performance.     

Effect of alcohol on recall and recognition as functions of processing levels

Other investigators have suggested that the memory impairments found in alcohol intoxication represent the failure to process information to sufficient depth, i.e., an encoding deficit. The present study employed different processing levels (semantic, phonemic and graphemic) in intentional-learning experiments to examine the effects of two different doses of alcohol on verbal free recall and recognition. Alcohol significantly impaired both recall and recognition. Guiding processing at information input with semantic orienting tasks and at retrieval with recognition testing improved the retention performance of both intoxicated subjects and controls administered a placebo. However, neither procedure corrected the relative decrement associated with the higher of the two doses of alcohol. Alcohol intoxication had no effect on the speed or accuracy of the initial encoding of items at any processing level. The results offer no support for the view that the verbal-retention deficits associated with alcohol intoxication are related either to the spontaneous failure to undertake deep semantic processing or to the inability to do so.     

Acute Effects of Temazepam and Nitrazepam on Psychomotor Skills and Memory

Abstract Twelve pretrained healthy students ingested temazepam, nitrazepam, and placebo, each double blind at one-week intervals in randomized order. Reactive and co-ordinative skills and critical flicker fusion were measured before each drug intake and 1,2,3,6 and 8 hours after it. Short-term memory and paired association learning were measured at 1, 3 and 8 hours. The psychomotor responses to drugs were modified by a sequence effect (not at zero tests) which effect varied depending on the drug and parameter. In multivariance analysis it was included to reveal drug effects. Nitrazepam 10 mg increased reaction and co-ordination errors and also impaired learning and memory. Temazepam 10 mg impaired co-ordinative skills; on a whole it differed from nitrazepam but hardly from placebo. Temazepam 20 mg impaired co-ordination, and learning and memory. Both temazepam 20 mg and nitrazepam were experienced sedative. All drug effects were clearest during the first 3 hours, nitrazepam also impaired learning at 8 hours. Temazepam 20 mg seems suitable as a hypnotic.     

Scopolamine and lorazepam exert different patterns of effects in a test battery assessing stages of information processing

The effects of a single dose of scopolamine (0.5 mg) SC and of lorazepam (2.5 mg) PO were tested in two independent studies for their effects on performance in a psychometric battery which measured functions related to different stages of information processing. Attention and vigilance were measured by a continuous attention task and a vigilance task, respectively. Working memory and reasoning were evaluated by the rapid information processing and logical reasoning task; memory acquisition and storage were measured by pre- and post-drug immediate and delayed recall using visual material. The following pattern of effects was revealed: both scopolamine and lorazepam impaired performance in attentional and vigilance tasks as well as in the rapid information processing task significantly (P<0.05) when compared with their own placebo; in the logical reasoning task lorazepam significantly prolonged the time required to solve a problem; scopolamine did not have any effect on this task. Scopolamine impaired performance in the immediate recall but left delayed recall unaffected; lorazepam impaired only delayed recall, immediate recall remaining unaffected. These data suggest that scopolamine at this dose impaired mostly attention and early stages of information processes; lorazepam at the dose tested impaired also the later acquisition and encoding aspects of memory.This article is part of the Doctoral Thesis of B. Redemann     

An examination of differences in the time course of oxazepam's effects on implicit vs explicit memory

The present study was designed to examine the effects of oxazepam on implicit vs explicit memory processes, as a function of this drug's time course. The effects of oxazepam (30 mg) or placebo on directly comparable tests of implicit memory (word stem completion) and explicit memory (cued recall) were examined at three time points: 100 min post-drug administration (prior to the theoretical peak plasma concentration of oxazepam; i.e.'pre-peak' condition), 170 min post-drug (close to theoretical peak; i.e. 'peak' condition) or 240 min post-drug (following theoretical peak: i.e. 'post-peak' condition). Sixty healthy volunteers were randomly assigned to either the drug condition or the placebo condition in a double-blind design and were tested on both memory tests at one of the three time points. In the 'pre-peak' condition, oxazepam impaired cued recall performance relative to placebo but did not impair priming. In the 'peak' condition, oxazepam impaired performance on both memory tasks. In the 'post-peak' condition, cued recall performance in the oxazepam group remained significantly impaired relative to placebo. However, oxazepam-induced impairments in priming were only marginal, suggesting that oxazepam-induced impairments in implicit memory processes begin to wane following theoretical peak drug concentrations. The fact that oxazepam-induced priming impairments were significant only when the word stem completion task was administered close to peak plasma concentrations, supports the hypothesis that benzodiazepines exert time-dependent effects on implicit memory processes. The results also support the theoretical distinction between implicit and explicit memory processes, since the directly comparable implicit and explicit tasks showed different impairment curves over time.     

State-dependent retrieval and midazolam

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 recency. 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 state-dependent 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 state-dependent 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 mg/kg) 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.     

Differential effects of total sleep deprivation on contextual and spatial memory: modulatory effects of modafinil

The aim of the present work was to investigate in mice the effects of a total 10-hr sleep deprivation on contextual (episodic-like) and spatial (reference) memory tasks. For that purpose, mice learned two consecutive discriminations (D1 and D2) in a 4-hole board involving either identical (Serial Spatial Discrimination, SSD) or distinct (Contextual Serial Discrimination, CSD) internal contextual cues. In a second step, we intended to assess the corrective effect of modafinil on memory impairments generated by sleep deprivation. Sleep deprivation was triggered through an alternative platform apparatus (water box), previously validated using EEG recording and spectral analysis.We showed that a 10-hr total sleep deprivation impaired the CSD task but not the SSD one. Moreover, the impairment of contextual memory in sleep-deprived animals was dose-dependently corrected by modafinil. Indeed, modafinil administered after the sleep deprivation period and 30 min before the test session restored a memory retrieval pattern identical to non sleep-deprived animals at the doses of 32 and 64 mg/kg, however not at 16 mg/kg.Results hereby evidence that the vigilance-enhancing drug modafinil is able to restore the contextual memory performance at a low dose as compared to other memory tasks, possibly by an enhancement of hippocampal activity known to be both involved in the processing of contextual information and impaired following our sleep deprivation procedure.     

Selective effects of clonidine and temazepam on attention and memory

The present study compared the effects of clonidine and temazepam on performance on a range of tasks aiming to assess the role of central noradrenergic mechanisms in cognitive function. Fifteen healthy volunteers (seven male, eight female), aged 18-25 years, took part in a five-period crossover study in which they received placebo, temazepam (15 and 30 mg) and clonidine (150 and 300 microg) by mouth in counterbalanced order in sessions at least 4 days apart. A test battery was administered before treatment and at 45, 90 and 135 min after the dose. Performance on most tests was significantly impaired in a dose-related fashion, and subjective sedation was recorded for both drugs. The greatest impairments with clonidine were on attention in the presence of distractors. Clonidine did not affect the formation of new long-term memories, in contrast to temazepam, but did impair measures of working memory. Subjective effects, especially feelings of drunkenness and abnormality, were particularly marked with clonidine. These results support the suggestion that central noradrenergic function may be involved in preventing distraction, but do not confirm other reports suggesting that some aspects of performance are improved with clonidine.     

Errors in performance testing: a comparison of ethanol and temazepam

Both ethanol and benzodiazepines impair psychomotor function. Previous work has suggested that ethanol may have a greater effect on errors while benzodiazepines may cause greater slowing, but this has not been tested in a direct comparison. We assessed the effects of ethanol, at blood concentrations of approximately 80-100 mg/100 ml, compared to two doses of temazepam (20 mg and 30 mg) on psychomotor speed and accuracy and on long-term memory. Sixteen healthy volunteers (eight male, aged 20-25 years) took part in a four-period, placebo-controlled cross-over study. Performance was evaluated using analysis of covariance (critical significance level, p = 0.05) comparing the areas under the response-time curves. Performance on a psychomotor maze showed an almost complete dissociation, with ethanol leading to a substantial and significant increase in errors with little effect on speed, while temazepam slowed performance with no significant change in accuracy. Other tasks showed a similar pattern, but the dissociation was less complete. Handwriting size was substantially increased by ethanol, but not by temazepam. Information processing capacity and long-term memory formation were reduced by a similar amount both for ethanol and 30 mg temazepam. The faster, more error-prone, behaviour on ethanol than with a similarly impairing dose of temazepam has clear implications for the relative potential of the two drugs to contribute to accidents. The results are also important in understanding the differential effects of drugs with different mechanisms of action on human performance.     

Effects of a benzodiazepine on free recall of semantically related words

Although it is widely known that benzodiazepines impair episodic memory, few studies have investigated their effects upon specific processes involved in free recall. This study evaluated the acute effects of flunitrazepam (1.0 mg; 1.3 mg) and placebo in healthy volunteers on immediate and delayed free recall of word lists considering serial positions as well as semantic relations between words inserted in the middle of the lists (e.g. milk-cheese-butter). Flunitrazepam promoted a global amnestic effect, impairing recall in all serial positions except the last words (recency effect). Primacy and recency effects were preserved as indexed, respectively, by larger recall of the first and last words in relation to adjacent items. Facilitation in recall of semantically related words was not impaired by the drug when compared to recall in adjacent positions, in spite of a dose-dependent diminution of the number of words recalled also in mid-list positions. Flunitrazepam-induced deficits were interpreted as impairment in the formation of new associations between items, or groups of items in the case of related words, and context.     

Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788

A combined visual (pictures) and auditory (word lists) memory test developed to trace the course of information processing under pharmacological or other influences was validated in a group of 20 subjects (control group) and then applied to determine the amnesic effects of lormetazepam and the reversal of these effects by the benzodiazepine antagonist Ro 15-1788. Three groups of n=10 subjects received either 0.02 mg/kg IV lormetazepam (groups B and C) or placebo (group A) followed 14 min later by 0.03 mg/kg IV Ro 15-1788 (groups A and C) or placebo (group B). The time course of memory performance in the three groups was investigated and compared across three consecutive 14-min phases: before (phase 1) and after (phase 2) the first intravenous administration, and after the second treatment (phase 3). Results were also compared with those of 20 subjects from a drug-free control group in order to verify the memory test. Lormetazepam clearly impaired immediate and delayed free recall as well as recognition in both visual and auditory tasks. These effects were completely reversed by Ro 15-1788, which alone had no clear effect on memory performance in this study. Psychometric scales indicated concomitant sedation and impaired concentration after lormetazepam alone. Interestingly, lormetazepam retrogradely enhanced performance in the visual test of delayed free recall. The impaired acquisition of new information after the administration of lormetazepam may be associated with an improvement of the consolidation process of information acquired before drug treatment.This article is part of the doctoral thesis of Dagmar Berenberg     

State-dependent effects of alcohol on recollective experience, familiarity and awareness of memories

RATIONALE: Explicit memory (EM) is the memory for events which occurs with full awareness of where and how the recalled events took place, whereas implicit memory (IM) is the memory which is unfolded without any awareness of these events and usually becomes apparent when performance is facilitated by its presence. These two types of memory can be understood as different systems. Findings attempting to differentiate between the two systems in normal subjects have been controversial, with some researchers arguing that there is a single memory system and only the match in processes used during learning and later at retrieval can be important. OBJECTIVES: The present study compared the effects of alcohol (0.8 g/kg) or placebo administered prior to encoding and/or retrieval on measures of explicit and implicit memory in terms of recollective experience and familiarity. METHODS: At encoding subjects studied a list of 80 words presented in pairs. At retrieval, participants first carried out an implicit stem completion task, followed by an explicitly cued recall task (stem completion) which measured IM and EM respectively. After stem completion participants were required to indicate whether the items from the studied list were consciously recollected ("remember" response) or was known for a fact that were presented in the studied list ("know" response). In the IM task completed items from the studied list but not recognised by the subjects as such indicated memory without awareness. Studied items were of high and low associations. Forty-eight participants were tested in one of four drug conditions: alcohol-alcohol, placebo-placebo, placebo-alcohol, alcohol-placebo. RESULTS: In the implicit stem completion task, alcohol did not affect overall correct completion rates. However, participants who received alcohol prior to encoding reported lower awareness of correctly completed study items. In the cued recall task, alcohol also did not affect overall performance. However, participants in the same drug-state conditions (SS) reported greater recollection than familiarity with study material, whereas participants who encoded and retrieved material in different drug-state conditions (DS) reported recollection and familiarity to the same extent. In addition, DS participants showed more familiarity with study material compared to SS participants. Direct comparisons between IM and EM tasks demonstrated that alcohol at retrieval decreased the cued recall of items from high associations compared to placebo, but did not have any effect on implicit stem completion. CONCLUSIONS: In summary, these results demonstrate a dissociation of alcohol effects on measures of EM and IM. Alcohol administered prior to encoding reduced awareness of implicitly retrieved material, but did not impair IM per se, confirming previous findings with alcohol. In addition, the data provided new evidence for state-dependent retrieval effects on EM but not IM. It was also shown that for explicitly retrieved items, recollective experience benefits from same drug state, whereas familiarity benefits from different drug state between encoding and retrieval.     

Marijuana effects on long-term memory assessment and retrieval

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg·delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.     

Nicotinic and muscarinic receptors in the rat prefrontal cortex: Differential roles in working memory,response selection and effortful processing

The aim of the present study was to evaluate the effects of cholinergic receptor blockade in the rat prefrontal cortex on cognitive processes. The nicotinic antagonists neuronal bungarotoxin and dihydro--erythroidine and the muscarinic antagonist scopolamine were injected into the prelimbic area of the prefrontal cortex. Their behavioural effects were assessed in a T-maze to test reference memory (visual discrimination task) and working memory in delayed matching (MTS) and non-matching to sample (NMTS) tasks. Neuronal bungarotoxin produced a significant decrease in working memory performance in the MTS task but not in the NMTS task. In contrast, scopolamine impaired working memory in both MTS and NMTS tasks. Reference memory was not altered by any of the cholinergic antagonists. These results demonstrate a differential role of nicotinic and muscarinic receptors in the rat prefrontal cortex. Nicotinic transmission appears to be important in delayed response tasks requiring effortful processing for response selection, while the muscarinic system is involved in general working memory processes.     

Alcohol enhancement of human memory: Tests of consolidation and interference hypotheses

Two hypotheses about the phenomenon of alcoholenhanced human memory were investigated. Whereas a consolidation account of this phenomenon indicates that continued processing of a target memory is facilitated by alcohol, an interference account states that the alcohol main effect is to impair the acquisition of potentially interfering new memories. No support was found for the consolidation view in an experiment manipulating (1) the length of time items preceded drug administration, (2) the amount of postpresentation processing each item received, and (3) the type of memory test employed. In line with expectations derived from interference theory, retention was substantially improved only for recall and not for tests of recognition memory.