The role of nociceptin in cognition.

The physiological role of the modulation via the nociceptin receptor is still unclear. Here we report the role of the nociceptin system in learning and memory. Nociceptin-knockout mice possess greater learning ability in the water maze task, show an enhanced latent learning in the water finding task, have better memory in the passive avoidance task, and further, show larger long-term potentiation in the hippocampal CA1 region than wild-type mice. Nociceptin itself induces an impairment of the passive avoidance task in wild-type mice. This impairment is reversed by naloxone benzoylhydrazone (NalBzoH), but not by other opioids in wild-type mice. Further, experiments on cultured cells transfected with nociceptin receptor cDNA show that NalBzoH competes [3H]-nociceptin binding and attenuates the nociceptin-induced inhibition of cAMP accumulation induced by forskolin. These results demonstrate that the nociceptin system seems to play a negative role in learning and memory and that NalBzoH acts as a potent antagonist for the nociceptin receptor. In addition, the antagonists for the nociceptin receptor may be worth testing for alleviating memory disorders.