[Nphe(1)]-Nociceptin (1-13)-NH2, 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 e ects of the novel nociceptin receptor antagonist, [Nphe1]-Nociceptin (1-13)-NH2 (bilateral intrahippocampal injection, 50 nmole rat71) on purported nociceptin-induced (bilateral intrahippocampal injection, 5 nmole rat71) de®cits in spatial learning in the rat Morris water maze task. In addition, experiments were performed in an `open ®eld' to investigate possible peptide-induced changes in exploratory behaviour. 2 Nociceptin signi®cantly impaired the ability of the animal to locate the hidden platform throughout training (P50.001 versus control group). 3 Pretreatment with [Nphe1]-Nociceptin (1-13)-NH2 signi®cantly blocked nociceptin-induced impairment of spatial learning (P50.001 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-speci®c de®cits in motor performance or change in exploratory behaviour. 6 Taken together, our results reveal that [Nphe1]-Nociceptin (1-13)-NH2 represents an e ective and useful in vivo antagonist at the nociceptin receptors involved in learning and memory.