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

Abstract

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 60min after injection, the subjects underwent an automated computerized battery of 1 1 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 enviroilmental 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.KEY worn-Scopolamine, cholinergic system, human cognition, attention, information processing, memory, automated cognitive test battery, cholinergic hypothesis of geriatric memory loss.

Blockade of Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task.

“…The delay durations ranged between 30 and 50 min (due to slight variation in length of medical examinations and injection procedures), were held constant within subject for Phases 1 and 2 of the study, and were similar overall in the three groups. These time periods coincide with the time course for the onset of the amnestic side effects of scopolamine in young healthy subjects (Bishop, Curran, & Lader, 1996;Dundee & Pandit, 1972;Ebert, Siepmann, Oertel, Wesnes, & Kirch, 1998;Pandit & Dundee, 1970;Safer & Allen, 1971;Wesnes, Simpson, & Kidd, 1988). During the delay periods, subjects performed distractor tasks to avoid rehearsal of the word pairs.…”

Differential effects of scopolamine and lorazepam on working memory maintenance versus manipulation processes

“…Successive sessions were separated by a minimum of 48 h. Single doses of placebo, 1.0 mg/70 kg lorazepam, 2.0 mg/70 kg lorazepam, 0.25 mg/70 kg scopolamine, and 0.50 mg/70 kg scopolamine were administered across the five sessions in a double-blind (i.e., both the participant and the staff member directly involved in data collection were blind to specific drug conditions in order to minimize the confounding of data by expectations about the nature of drug effects), within-subjects crossover design. Lorazepam was administered orally and scopolamine was administered subcutaneously, as in previous studies, due to its more variable absorption rate after oral administration (Bishop et al, 1996;Mintzer & Griffiths, 2001a, 2003Wesnes, Simpson, & Kidd, 1988). Given that scopolamine and lorazepam were administered by different routes, in order to further mask the drug condition, drug administration was "double dummy," such that participants received both an oral dose (of either lorazepam or lactose placebo capsules ingested with approximately 150 ml of water) and a subcutaneous injection (of either scopolamine or saline placebo; administered in a constant volume of 1 ml in the upper right arm) during each session.…”

Safety, Pharmacokinetics, and Effects on Cognitive Function of Multiple Doses of GTS-21 in Healthy, Male Volunteers

“…Using computerized tests developed by Cognitive Drug Research Ltd (CDR) (Reading, UK), changes in attention, memory and reaction time from predose measurements were assessed during each session (Wesnes et al, 1988). Cognitive tests included the following: attention-related tests (simple reaction time, choice reaction time, digit vigilance), numeric and spatial working memory tests, secondary episodic recognition memory tests (word and picture recognition, immediate and delayed word recall) and visual tracking.…”