Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task

Behav Brain Res. 2006 Oct 2;173(1):47-52. doi: 10.1016/j.bbr.2006.05.028. Epub 2006 Jul 3.

Abstract

Orexin containing neurons in the lateral hypothalamic area (LHA) produce orexin-A (hypocretin-1) and orexin-B (hypocretin-2) and send their axons to the hippocampus, which predominantly expresses orexin 1 receptors (OX1Rs) showing a higher affinity to orexin-A. Recent studies have shown that central administration of orexin-A has an effect on learning and memory but literature concerning the role of orexinergic system in cognition remains controversial. Therefore, we examined the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of a selective OX1R the orexin 1 receptor antagonist SB-334867-A (1.5, 3, 6 microg/0.5 microl) on acquisition, consolidation and retrieval in a single-day testing version of Morris water maze (MWM) task. Our results show that, SB-334867-A impaired acquisition, consolidation and retrieval of MWM task as compared with the control group. This drug had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexins, especially orexin-A, play an important role in spatial learning and memory in the rat.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzoxazoles / administration & dosage
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology*
  • Dose-Response Relationship, Drug
  • Escape Reaction / drug effects
  • Hippocampus / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Microinjections
  • Naphthyridines
  • Neuropeptides / physiology*
  • Orexin Receptors
  • Orexins
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / metabolism*
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology*
  • Urea / administration & dosage
  • Urea / analogs & derivatives

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Hcrtr1 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Naphthyridines
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Urea