The nociceptin system and hippocampal cognition in mice: a pharmacological and genetic analysis.
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.
Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Alexander
A
Kuzmin
Nather
N
Madjid
Björn
B
Johansson
Lars
L
Terenius
Sven Ove
SO
Ogren
D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D009483:Neuropsychological Tests; D018847:Opioid Peptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002491:Central Nervous System Agents; D007093:Imidazoles; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C408068:Ro 64-6198; C439964:nociceptin (1-13) amide; C121527:prepronociceptin; C058380:naloxone benzoylhydrazone; C000722287:Oprl1 protein, mouse