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

Article date: December 2000

By: J P Redrobe, G Calo, R Guerrini, D Regoli, R Quirion in Volume 131, Issue 7, pages 1379-1384

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.

Nociceptin significantly impaired the ability of the animal to locate the hidden platform throughout training (P<0.001 versus control group).

Pretreatment with [Nphe1]‐Nociceptin (1‐13)‐NH2 significantly blocked nociceptin‐induced impairment of spatial learning (P<0.001 versus nociceptin group).

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.

Learning impairments were not attributable to non‐specific deficits in motor performance or change in exploratory behaviour.

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.

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.

Nociceptin significantly impaired the ability of the animal to locate the hidden platform throughout training (P<0.001 versus control group).

Pretreatment with [Nphe1]‐Nociceptin (1‐13)‐NH2 significantly blocked nociceptin‐induced impairment of spatial learning (P<0.001 versus nociceptin group).

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.

Learning impairments were not attributable to non‐specific deficits in motor performance or change in exploratory behaviour.

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.

British Journal of Pharmacology (2000) 131, 1379–1384; doi:10.1038/sj.bjp.0703724

DOI: 10.1038/sj.bjp.0703724

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