[Nphe1]-Nociceptia (1-13)-NH2, a nociceptin receptor antagonist, reverses nociceptin-induced spatial memory impairments in the Morris water maze task in rats

Abstract

1. The present study was undertaken to investigate the effects of the novel nociceptin receptor antagonist, [Nphe1]-Nociceptin (1-13)-NH2 (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 [Nphe1]-Nociceptin (1-13)-NH2 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 [Nphe1]-Nociceptin (1-13)-NH2 represents an effective and useful in vivo antagonist at the nociceptin receptors involved in learning and memory.