The role of nociceptin in cognition

The physiological role of the modulation via the nociceptin receptor is sti ll unclear. Here we report the role of the nociceptin system in learning an d 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 large r long-term potentiation in the hippocampal CA1 region than wild-type mice. Nociceptin itself induces an impairment of the passive avoidance task in w ild-type mice. This impairment is reversed by naloxone benzoylhydrazone (Na lBzoH), but not by other opioids in wild-type mice. Further, experiments on cultured cells transfected with nociceptin receptor cDNA show that NalBzoH competes [H-3]-nociceptin binding and attenuates the nociceptin-induced in hibition of cAMP accumulation induced by forskolin. These results demonstra te 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 rec eptor. in addition, the antagonists for the nociceptin receptor may be wort h testing for alleviating memory disorders. (C) 1999 Elsevier Science B.V. All rights reserved.