FACILITATION OF LONG-TERM POTENTIATION AND MEMORY IN MICE LACKING NOCICEPTION RECEPTORS

The peptide nociceptin (also named orphanin FQ) acts in the brain to p roduce various pharmacological effects, including hyperalgesia and hyp olocomotion(1,2). The nociceptin receptor uses guanine-nucleotide-bind ing proteins to mediate the inhibition of adenylyl cyclase, the activa tion of potassium channels and inhibition of calcium channels(3). It h as been shown using knockout mice that the nociceptin receptor is not required for regulation of nociceptive responses or locomotion activit y, but modulates the auditory function(4). Here we show that mice lack ing the nociceptin receptor possess greater learning ability and have better memory than control mice. Histological analysis revealed the ex pression of both the nociceptin precursor and the nociceptin receptor in the hippocampus, thought to take part in aspects of learning and me mory. Moreover, the receptor-deficient mice showed larger long-term po tentiation in the hippocampal CAI region than control mice, without ap parent changes in presynaptic or postsynaptic electrophysiological pro perties. These results show that the loss of the nociceptin receptor r esults in a gain-of-function mutation in both the memory process and t he long-term potentiation mechanism in CA1, perhaps as a result of alt ered intracellular signal transduction systems in neurons.