Facilitation of long-term potentiation and memory in mice lacking nociception receptors

被引:281
作者
Manabe, T
Noda, Y
Mamiya, T
Katagiri, H
Houtani, T
Nishi, M
Noda, T
Takahashi, T
Sugimoto, T
Nabeshima, T
Takeshima, H [1 ]
机构
[1] Univ Tokyo, Fac Med, Dept Pharmacol, Bunkyo Ku, Tokyo 1138654, Japan
[2] Univ Tokyo, Fac Med, Dept Neurophysiol, Bunkyo Ku, Tokyo 1138654, Japan
[3] Nagoya Univ, Sch Med, Dept Neuropsychopharmacol, Nagoya, Aichi 4668560, Japan
[4] Nagoya Univ, Sch Med, Hosp Pharm, Nagoya, Aichi 4668560, Japan
[5] Kansai Med Univ, Dept Anat, Osaka 5708506, Japan
[6] Inst Canc, Dept Cell Biol, Toshima Ku, Tokyo 1708455, Japan
关键词
D O I
10.1038/29073
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The peptide nociceptin (also named orphanin FQ) acts in the brain to produce various pharmacological effects, including hyperalgesia and hypolocomotion(1,2). The nociceptin receptor uses guanine-nucleotide-binding proteins to mediate the inhibition of adenylyl cyclase, the activation of potassium channels and inhibition of calcium channels(3). 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(4). Here we show 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 CAI 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.
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页码:577 / 581
页数:5
相关论文
共 29 条
  • [1] DIRECT INVIVO GENE-TRANSFER TO EPENDYMAL CELLS IN THE CENTRAL-NERVOUS-SYSTEM USING RECOMBINANT ADENOVIRUS VECTORS
    BAJOCCHI, G
    FELDMAN, SH
    CRYSTAL, RG
    MASTRANGELI, A
    [J]. NATURE GENETICS, 1993, 3 (03) : 229 - 234
  • [2] A SYNAPTIC MODEL OF MEMORY - LONG-TERM POTENTIATION IN THE HIPPOCAMPUS
    BLISS, TVP
    COLLINGRIDGE, GL
    [J]. NATURE, 1993, 361 (6407) : 31 - 39
  • [3] Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region
    Blitzer, RD
    Wong, T
    Nouranifar, R
    Iyengar, R
    Landau, EM
    [J]. NEURON, 1995, 15 (06) : 1403 - 1414
  • [4] EFFECTS OF CAMP SIMULATE A LATE-STAGE OF LTP IN HIPPOCAMPAL CA1 NEURONS
    FREY, U
    HUANG, YY
    KANDEL, ER
    [J]. SCIENCE, 1993, 260 (5114) : 1661 - 1664
  • [5] Activation of mitogen-activated protein kinase by the nociceptin receptor expressed in Chinese hamster ovary cells
    Fukuda, K
    Shoda, T
    Morikawa, H
    Kato, S
    Mori, K
    [J]. FEBS LETTERS, 1997, 412 (02) : 290 - 294
  • [6] The orphan opioid receptor and its endogenous ligand-nociceptin/orphanin FQ
    Henderson, G
    McKnight, AT
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1997, 18 (08) : 293 - 300
  • [7] Structure and regional distribution of nociceptin/orphanin FQ precursor
    Houtani, T
    Nishi, M
    Takeshima, H
    Nukada, T
    Sugimoto, T
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 219 (03) : 714 - 719
  • [8] PROTEIN-KINASE-C INJECTION INTO HIPPOCAMPAL PYRAMIDAL CELLS ELICITS FEATURES OF LONG-TERM POTENTIATION
    HU, GY
    HVALBY, O
    WALAAS, SI
    ALBERT, KA
    SKJEFLO, P
    ANDERSEN, P
    GREENGARD, P
    [J]. NATURE, 1987, 328 (6129) : 426 - 429
  • [9] Functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated K+ (GIRK) channel
    Ikeda, K
    Kobayashi, K
    Kobayashi, T
    Ichikawa, T
    Kumanishi, T
    Kishida, H
    Yano, R
    Manabe, T
    [J]. MOLECULAR BRAIN RESEARCH, 1997, 45 (01): : 117 - 126
  • [10] Knoflach F, 1996, J NEUROSCI, V16, P6657