Abstract
This study examines the effects of NOP agonists nociceptin/orphanin FQ (N/OFQ) and Ro 64-6198, NOP antagonists [Nphe(1)]N/OFQ(1-13)-NH(2) Nphe(1) and naloxone benzoylhydrazone (NalBzoH) on spatial memory in NMRI mice and pronociceptin (proNC) knockout (KO) mice using the water maze task. N/OFQ, administered i.c.v. (1, 5 and 10 nmol/mouse) and into hippocampal CA3 (1 nmol/mouse, bilaterally), impaired acquisition and retention in the maze. Impairments were blocked by pre-treatment with Nphe(1) (10 nmol, i.c.v.). Ro 64-6198 (0.1-0.3-1 mg/kg i.p.) also dose-dependently impaired learning. However, pre-treatment with NalBzoH (1 mg/kg, s.c.) failed to modify the effects of Ro 64-6198. Nphe(1) (10 nmol/mouse i.c.v.) and NalBzoH (1 mg/kg, s.c.) by themselves failed to affect maze performance, despite a tendency for enhanced performance. Prepro N/OFQ knockout (ppN/OFQ -/-) showed evidence of improved learning, evident at retention trials and in reversal training. ppN/OFQ -/- mice were not impaired by N/OFQ (10 nmol i.c.v.) in the task, suggesting that changes in postsynaptic NOP receptors may occur in such KO mice. It is concluded that N/OFQ and NOP receptors have an important role in hippocampus-dependent spatial learning and memory, probably by modulation of glutamatergic functions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Central Nervous System Agents / administration & dosage
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Central Nervous System Agents / pharmacology
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Cognition / drug effects
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Cognition / physiology*
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Dose-Response Relationship, Drug
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Hippocampus / drug effects
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Hippocampus / physiology*
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Imidazoles / administration & dosage
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Imidazoles / pharmacology
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Male
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Maze Learning / drug effects
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Maze Learning / physiology*
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Memory / drug effects
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Memory / physiology*
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Naloxone / administration & dosage
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Naloxone / analogs & derivatives
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Naloxone / pharmacology
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Narcotic Antagonists
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Neuropsychological Tests
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Nociceptin
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Nociceptin Receptor
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Opioid Peptides / metabolism*
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Peptide Fragments / metabolism
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Protein Precursors / genetics
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Protein Precursors / metabolism
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Random Allocation
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Receptors, Opioid / agonists
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Receptors, Opioid / genetics
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Receptors, Opioid / metabolism*
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Reversal Learning / drug effects
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Reversal Learning / physiology
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Spiro Compounds / administration & dosage
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Spiro Compounds / pharmacology
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Time Factors
Substances
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Central Nervous System Agents
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Imidazoles
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Narcotic Antagonists
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Opioid Peptides
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Peptide Fragments
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Protein Precursors
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Receptors, Opioid
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Ro 64-6198
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Spiro Compounds
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nociceptin (1-13) amide
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prepronociceptin
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naloxone benzoylhydrazone
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Naloxone
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Nociceptin Receptor
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Oprl1 protein, mouse