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Psychopharmacology (Berl). 2013 Aug;228(4):673-83. doi: 10.1007/s00213-013-3072-2. Epub 2013 Apr 9.

Effect of cholinergic neurotransmission modulation on visual spatial paired associate learning in healthy human adults.

Author information

1
CogState, Ltd, 195 Church St., 8th Floor, New Haven, CT 06510, USA. bharel@cogstate.com

Abstract

RATIONALE:

Use of cross-species neuropsychological paradigms such as visual-spatial paired associate learning (PAL) may allow for a better understanding of underlying neural substrates of memory. Such paradigms, which are often used to guide models of memory in animals, can then be carried forward into humans to provide a basis for evaluation of pharmacologic compounds designed to ameliorate learning and memory impairments in neurologic and psychiatric morbidities.

OBJECTIVES:

This double-blind, randomized, crossover trial investigated effects of donepezil, an acetylcholinesterase (AChE) inhibitor, in attenuating scopolamine-induced cognitive impairment using a novel, "process-based" computerized measure of visual-spatial PAL.

RESULTS:

In healthy male volunteers, scopolamine (0.6 mg) induced a time-dependent reduction in visual-spatial PAL, with the greatest impairment (Cohen's d = 1.37) observed 2 h after dosing. Cotreatment with donepezil (10 mg) significantly ameliorated scopolamine-induced impairment at the 2-h time point (Cohen's d = 0.66). Process-based analyses revealed a significant impairment in both memory (Cohen's d = 1.37 to 0.50) and executive (Cohen's d = 1 .21 to 0.62) aspects of visual-spatial PAL performance following acute scopolamine challenge, and these reductions were ameliorated by donepezil.

CONCLUSIONS:

Acute scopolamine challenge can produce large and robust deficits in visual-spatial PAL, which reflect impairments in both memory and executive processes. Coadministration of a single dose of donepezil can ameliorate these deficits. These results provide support for the use of a visual-spatial PAL test as a pharmacodynamic cognitive marker of central nervous system (CNS)-mediating compounds in humans.

PMID:
23568575
DOI:
10.1007/s00213-013-3072-2
[Indexed for MEDLINE]

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