The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze
- 31 March 2007
- journal article
- Published by Elsevier BV in Peptides
- Vol. 28 (3), 650-656
- https://doi.org/10.1016/j.peptides.2006.11.002
Abstract
The novel neuropeptides orexin-A and orexin-B derive from a common 130-amino acid precursor molecule (prepro-orexin), are mainly localized to neurons within and around the lateral hypothalamus, and exhibit high affinity to the closely related G-Protein-coupled receptors orexin 1 and 2 receptor (OX1R, OX2R). Orexinergic neurons send their axons to the hippocampal formation (CA1, CA2 and dentate gyrus), which expresses OX1Rs. Recent studies have shown that central administration of orexin-A and orexin-B have effects on learning and memory but literature concerning the role of orexinergic system in cognition remains controversial. More recently, antagonists have been described. The most potent and selective is SB-334867-A, which has an affinity of 40 nM at OX1R which is at least 50-fold selective over OX2R. It is likely that the intracerebroventricular (i.c.v.) administration may block OX1Rs in many brain regions. Previously we have shown that intra-CA1 injection of SB-334867-A impairs acquisition, consolidation and retrieval of spatial memory in MWM task. In the present study, the effect of pre-training, post-training and pre-probe of trial intra-DG (dentate gyrus) administration of SB-334867-A (1.5, 3, 6 μg/0.5 μl) on acquisition, consolidation and retrieval in a single-day testing version of MWM (Morris water maze) task was examined. Our results show impaired acquisition and consolidation of MWM task for SB-334867-A as compared with the control group. However, SB-334867-A had no effect on retrieval in spatial memory. Also, this antagonist had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexin-A and orexin-B, through DG OX1Rs, play an important role in spatial learning and memory in the rat.Keywords
This publication has 48 references indexed in Scilit:
- Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze taskBehavioural Brain Research, 2006
- G-protein-coupled OX1 Orexin/hcrtr-1 Hypocretin Receptors Induce Caspase-dependent and -independent Cell Death through p38 Mitogen-/Stress-activated Protein KinasePublished by Elsevier BV ,2006
- Orexin-A (hypocretin-1) impairs Morris water maze performance and CA1-Schaffer collateral long-term potentiation in ratsNeuroscience, 2003
- Molecular Psychology: Roles for the ERK MAP Kinase Cascade in MemoryAnnual Review of Pharmacology and Toxicology, 2002
- Orexin-A, an hypothalamic peptide with analgesic propertiesPain, 2001
- Orexins, feeding and the big pictureBritish Journal of Nutrition, 2000
- Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systemsProceedings of the National Academy of Sciences of the United States of America, 1999
- The MAPK cascade is required for mammalian associative learningNature Neuroscience, 1998
- The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activityProceedings of the National Academy of Sciences of the United States of America, 1998
- A synaptic model of memory: long-term potentiation in the hippocampusNature, 1993