Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

Abstract

During Year 2, a new laboratory for behavioral performance assessment and microdialysis sampling was occupied and two new HPLCs were purchased and calibrated. Both the benzodiazepine receptor agonist zolpidem (ZOL) and the hypocretin (Hcrt) receptor antagonist almorexant (ALM) induced sleep in rodents. However, ALM did not impair performance in a spatial reference memory test whereas ZOL did. Preliminary results indicate that the wake-active Hcrt neurons could be activated in the presence of ALM but not in the presence of ZOL. In contrast, a sleep-active cortical neuron population was equally activated by ALM and ZOL. ALM caused a significant decrease in basal forebrain (BF) glutamate and concurrently increased BF GABA and adenosine during NREM/REM sleep compared to ZOL or VEH. These results are consistent withthe hypothesis that the disfacilitation of wake-promoting systems by ALM results in less functional impairment than the general inhibition of neural activity produced by ZOL.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2011
Accession Number
ADA552886

Entities

People

  • Thomas Kilduff

Organizations

  • SRI International

Tags

DTIC Thesaurus Topics

  • Adenosine
  • Amino Acids
  • Arousal (Physiology)
  • Brain
  • Cerebral Cortex
  • Chemistry
  • Data Analysis
  • Data Science
  • Descriptive Analytics
  • Electronic Mail
  • Flow Rate
  • Glutamates
  • Information Science
  • Neurons
  • Neurophysiology
  • Neurosciences
  • Sampling

Fields of Study

  • Biology
  • Psychology

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  • Circadian Sleep-Wake Regulation and Chronobiology
  • Inertial Navigation Systems.
  • Neuroscience