Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task.
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.
Akbari
Esmaeil
E
Neuroscience Research Center and Department of Physiology, School of Medicine, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Naghdi
Nasser
N
Motamedi
Fereshteh
F
D000704:Analysis of Variance; D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009287:Naphthyridines; D009479:Neuropeptides / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives
C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014508:Urea