[Nphe(1)]-Nociceptin (1-13)-NH(2), a nociceptin receptor antagonist, reverses nociceptin-induced spatial memory impairments in the Morris water maze task in rats.
1. The present study was undertaken to investigate the effects of the novel nociceptin receptor antagonist, [Nphe(1)]-Nociceptin (1-13)-NH(2) (bilateral intrahippocampal injection, 50 nmole rat(-1)) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat(-1)) deficits in spatial learning in the rat Morris water maze task. In addition, experiments were performed in an 'open field' to investigate possible peptide-induced changes in exploratory behaviour. 2. Nociceptin significantly impaired the ability of the animal to locate the hidden platform throughout training (P<0.001 versus control group). 3. Pretreatment with [Nphe(1)]-Nociceptin (1-13)-NH(2) significantly blocked nociceptin-induced impairment of spatial learning (P<0.001 versus nociceptin group). 4. A probe trial revealed that vehicle-treated animals spent more time in the quadrant that had previously contained the hidden platform, whereas nociceptin-treated animals did not spend more time in any one quadrant. 5. Learning impairments were not attributable to non-specific deficits in motor performance or change in exploratory behaviour. 6. Taken together, our results reveal that [Nphe(1)]-Nociceptin (1-13)-NH(2) represents an effective and useful in vivo antagonist at the nociceptin receptors involved in learning and memory.
Redrobe
J P
JP
Douglas Hospital Research Centre, Department of Psychiatry, McGill University, 6875 Blvd LaSalle, Verdun, QC, Canada, H4H 1R3.
Calo
G
G
Guerrini
R
R
Regoli
D
D
Quirion
R
R
D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000503:physiopathology / Q000517:prevention & control*; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid; D013028:Space Perception / Q000187:drug effects*; D013550:Swimming; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722285:Oprl1 protein, rat