[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

Abstract

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.

Figure 1

Effect of intrahippocampal injection of nociceptin and [Nphe¹]-Nociceptin (1-13)-NH₂ on escape latency in the Morris water maze task (hidden platform). Animals were microinjected with isotonic NaCl, 5 nmole nociceptin, 50 nmole [Nphe¹]-Nociceptin (1-13)-NH₂ or [Nphe¹]-Nociceptin (1-13)-NH₂/nociceptin. (A) Data are expressed as mean latency±s.e.mean (averaged over four trials per session; n=12). (B) Data are expressed as mean latency±s.e.mean of each trial (12 trials during training; n=12). ^**P<0.01, ^***P<0.001 versus NaCl; +P<0.05, ++P<0.01, +++P<0.001 versus nociceptin.

Figure 2

Effect of intrahippocampal injection of nociceptin and [Nphe¹]-Nociceptin (1-13)-NH₂ on escape latency in the Morris water maze task (probe trial). Animals were microinjected with isotonic NaCl, 5 nmole nociceptin, 50 nmole [Nphe¹]-Nociceptin (1-13)-NH₂ or [Nphe¹]-Nociceptin (1-13)-NH₂/nociceptin. Data are expressed as mean latency± s.e.mean (n=12). ^**P<0.01 versus NaCl.

Figure 3

Effect of intrahippocampal injection of nociceptin and [Nphe¹]-Nociceptin (1-13)-NH₂ on swim speed in the Morris water maze task (hidden platform). Animals were microinjected with isotonic NaCl, 5 nmole nociceptin, 50 nmole [Nphe¹]-Nociceptin (1-13)-NH₂ or [Nphe¹]-Nociceptin (1-13)-NH₂/nociceptin. Data are expressed as cumulative mean latency±s.e.mean (averaged over 12 trial training sessions; n=12).

Figure 4

Effect of intrahippocampal injection of nociceptin on escape latency in the Morris water maze task (visible platform). Animals were microinjected with isotonic NaCl, 5 nmole nociceptin, 50 nmole [Nphe¹]-Nociceptin (1-13)-NH₂ or [Nphe¹]-Nociceptin (1-13)-NH₂/nociceptin. Data are expressed as mean latency±s.e.mean (n=12).

Figure 5

Effect of intrahippocampal injection of nociceptin and [Nphe¹]-Nociceptin (1-13)-NH₂ on exploratory behaviour. Animals were microinjected with isotonic NaCl, 5 nmole nociceptin, 50 nmole [Nphe¹]-Nociceptin (1-13)-NH₂ or [Nphe¹]-Nociceptin (1-13)-NH₂/nociceptin. Data are expressed as mean±s.e.mean (n=12).