Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

Abstract

During Year 1, progress was made on establishment of the infrastructure and baseline parameters to facilitate the proposed studies. Construction was initiated on a 535 s.f. lab suite within the Animal Facility that will provide an optimal environment for execution of the proposed in vivo studies; we expect to occupy this laboratory next week. An Analytical Neurochemistry Facility was established in LB212 and 4 HPLCs were purchased, installed, calibrated and the minimal detection levels for measurement of several neurotransmitters were determined. Over 25 g of the test compound, the hypocretin receptor antagonist almorexant (ALM), was synthesized, resulting in achievement of the first milestone. The effects of 3 concentrations of ALM on sleep/wake, locomotor activity and body temperature were determined. The behavioral performance studies were initiated in a temporary location. We are now well-positioned to rigorously test the hypothesis in Years 2-4 that ALM produces fewer functional impairments than the benzodiazepine receptor agonist zolpidem (ZOL) because ZOL causes a general inhibition of neural activity whereas ALM specifically disfacilitates wake-promoting systems.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2010
Accession Number
ADA541998

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