|Budget Amount *help
¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Nociceptin, a novel neuropeptide, produces various pharmacological effects including hyperalgesia and hypolocomotion. At the cellular level, the nociceptin receptor mediates the inhibition of adenylate cyclase, the activation of potassium channels and inhibition of calcium channels by coupling with guanine-nucleotide-binding proteins. It has been shown using knockout mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activity, but modulates the auditory function. We have found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. In this study, we showed that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the expression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and memory. Moreover, the receptor-deficient mice showed larger long-term potentiation in the hippocampal CA1 region than control mice, without apparent changes in presynaptic or postsynaptic electrophysiological properties. These results show that the loss of the nociceptin receptor results in a gain-of-function mutation in both the memory process and the long-term potentiation mechanism in CA1, perhaps as a result of altered intracellular signal transduction systems in neurons.