Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant
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Published on: July 8, 2015
Hendrik Dietrich1, François Jenck
1Research and Development, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. hendrik.dietrich@actelion.com
Rationale:
Orexins play a key role in the maintenance of alertness and are implicated in the modulation of diverse physiological processes, including cognitive function. Almorexant, a dual orexin receptor antagonist, transiently and reversibly blocks the action of orexin peptides at both OX(1) and OX(2) receptors and increases time spent in rapid eye movement (REM) and non-REM sleep.
Objectives:
We explored the direct effects on learning and memory of single and repeated administration of almorexant in rats.
Methods:
Following administration of high doses of almorexant (300 mg/kg, p.o.), scopolamine (0.8 mg/kg, i.p.), combination almorexant-scopolamine, or vehicle alone, rats were trained on a Morris water maze spatial navigation task, or on a passive avoidance task.
Results:
Rats treated with almorexant learned the spatial navigation task with similar efficacy as vehicle-treated animals. After 4 days, almorexant-but not vehicle-treated rats had established spatial memory; after 8 days, spatial memory had been established in both vehicle-and almorexant-treated rats. Scopolamine-treated rats failed to learn the spatial task. Both vehicle-and almorexant-but not scopolamine-treated rats demonstrated passive avoidance learning. Almorexant did not ameliorate scopolamine-induced impairment of learning in either task.
Conclusions:
Rats treated with almorexant are fully capable of spatial and avoidance learning.
