Skip to main content
SpringerLink
Log in

Characterization of neuropeptide Y, Y2 receptor knockout mice in two animal models of learning and memory processing

  • Original Article
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Neuropeptide Y (NPY) and, in particular, the Y2 receptor subtype, has been suggested to be involved in learning and memory processing. However, the precise role of Y2 receptors in learning and memmory remains unclear. In the present study, mice lacking NPY Y2-type receptors were assessed in two animal models of learning and memory processing. We found that NPY Y −/−2 mice displayed a deficit on the probe trial in the Morris water maze task, whereas acquisition performance, swim speed, and visible platform performance did not differ significantly between groups. In addition, NPY Y −/−2 mice exhibited a marked deterioration in object memory 6 h, but not 1 h, following initial exposure in the object recognition test. Both groups of mice showed similar locomotor activity profiles in a low-stress, open field test. These data support the hypothesis that Y2 receptors are involved in the regulation of learning and memory processing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baldock P. A., Sainsbury A., Couzens M., Enriquez R. F., Thomas G. P., Gardiner E. M., and Herzog H. (2002) Hypothalamic Y2 receptors regulate bone formation. J. Clin. Invest. 109, 915–921.

    Article  PubMed  CAS  Google Scholar 

  • Bouchard P., Maurice T., St-Pierre S., Privat A., and Quirion R. (1997) Neuropeptide Y and calcitonin gene-related peptide attenuate learning impairments induced by MK-801 via a sigma receptor-related mechanism. Eur. J. Neurosci. 9, 2142–2151.

    Article  PubMed  CAS  Google Scholar 

  • Buckley T. J. and Gaffan D. (1998) Perirhinal cortex albation impairs visual object identification. J. Neurosci. 18, 2268–2275.

    PubMed  CAS  Google Scholar 

  • Colmers W. F. and Bleakman D. (1994) Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci. 17, 373–379.

    Article  PubMed  CAS  Google Scholar 

  • D’Hooge R. and De Deyn P. P. (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res. Rev. 36, 60–90.

    Article  PubMed  CAS  Google Scholar 

  • Dumont Y., Jacques D., St-Pierre J.A., and Quirion R. (1997) Neuropeptide Y receptor types in the mammalian brain: species differences and status in the human central nervous system, in Neuropeptide Y and Drug Development, Grundemar, L., and Bloom, S. R., eds., Academic Press, London, UK, pp. 57–86.

    Google Scholar 

  • Dumont Y., Jacques D., St-Pierre J. A., Tong Y., Parker R., Herzog H., and Quirion R. (2000) Neuropeptide Y, peptide YY and pancreatic polypeptide receptor proteins and mRNAs in mammalian brain, in Handbook of Chemical Neuroanatomy, vol 16, Quirion, R., Bjorklund, A., and Hokfelt, T., eds., Elsevier, London, UK, pp. 375–475.

    Google Scholar 

  • Ennaceur A. and Aggleton J. P. (1997) The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat. Behav. Brain Res. 88, 181–193.

    Article  PubMed  CAS  Google Scholar 

  • Ennaceur A. and Delacour J. (1988) A new one-trial test for neurobiological studies of memory in rats. I. Behavioral data. Behav. Brain Res. 31, 47–59.

    Article  PubMed  CAS  Google Scholar 

  • Ennaceur A., Neave N., and Aggleton J. P. (1996) Neurotoxic lesions of the perirhinal cortex do not mimic the behavioral effects of fornix transection in the rat. Behav. Brain Res. 80, 9–25.

    Article  PubMed  CAS  Google Scholar 

  • Flood J. F., Baker M. L., Hernandez E. N., and Morley J. E. (1989) Modulation of memory processing by neuropeptide Y varies with brain injection site. Brain Res. 503, 73–82.

    Article  PubMed  CAS  Google Scholar 

  • Flood J. F., Hernandez E. N., and Morley J. E. (1987) Modulation of memory processing by neuropeptide Y. Brain Res. 421, 280–290.

    Article  PubMed  CAS  Google Scholar 

  • Gallagher M., Burwell R., and Burchinal M. (1993) Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav. Neurosci. 107, 618–626.

    Article  PubMed  CAS  Google Scholar 

  • Gerlai R. (2001) Behavioral tests of hippocampal function: simple paradigms complex problems. Behav. Brain Res. 125, 269–277.

    Article  PubMed  CAS  Google Scholar 

  • Gray J. A. and Lalljee B. (1974) Sex differences in emotional behaviour in the rat: correlation between open-field defecation and active avoidance. Anim. Behav. 22, 856–861.

    Article  PubMed  CAS  Google Scholar 

  • Gustafson E. L., Smith K. E., Durkin M. M., Walker M. W., Gerald C., Weinshank R., and Branchek T. A. (1997) Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system. Mol. Brain Res. 46, 223–235.

    Article  PubMed  CAS  Google Scholar 

  • Heilig M. (1993) Neuropeptide Y in relation to behavior and psychiatric disorders, in The Biology of Neuropeptide Y and Related Peptides, Colmers, W. F., and Wahlesdtedt, C., eds., Humana Press, Totowa, NJ, pp. 511–554.

    Google Scholar 

  • Heilig M., McLeod S., Koob G. K., and Britton K. T. (1992) Anxiolytic-like effect of neuropeptide Y (NPY), but not other peptides in an operant conflict test. Regul. Pept. 41, 61–69.

    Article  PubMed  CAS  Google Scholar 

  • Heilig M., Soderpalm B., Engel J. A., and Widerlov E. (1989) Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology 98, 524–529.

    Article  PubMed  CAS  Google Scholar 

  • Kask A., Harro J., von Horsten S., Redrobe J. P., Dumont Y., and Quirion R. (2002) The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y. Neurosci. Biobehav. Rev. 26, 259–283.

    Article  PubMed  CAS  Google Scholar 

  • King P. J., Williams G., Doods H., and Widdowson P. S. (2000) Effect of a selective neuropeptide Y Y2 receptor antagonist, BIIE0246 on neuropeptide Y release. Eur. J. Pharmacol. 396, R1-R3.

    Article  PubMed  CAS  Google Scholar 

  • Kornecook T. J., Kippin T. E., and Pinel J. P. J. (1999) Basal forebrain damage and object-recognition in rats. Behav. Brain Res. 98, 67–76.

    Article  PubMed  CAS  Google Scholar 

  • Majlessi N. and Naghdi N. (2002) Impaired spatial learning in the Morris water maze induced by serotonin reuptake inhibitors. Behav. Pharmacol. 13, 237–242.

    PubMed  CAS  Google Scholar 

  • Michel M. C., Beck-Sickinger A., Cox H., Doods H. N., Herzog H., Larhammar D., et al. (1998) International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol. Rev. 50, 143–150.

    PubMed  CAS  Google Scholar 

  • Morley J. E. and Flood J. F. (1990) Neuropeptide Y and memory processing. Ann. N. Y. Acad. Sci. 611, 226–231.

    Article  PubMed  CAS  Google Scholar 

  • Morris R. G. M., Garrud P., Rawlins J. N. P., and O’Keefe J. (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima M., Inui A., Teranishi A., Miura M., Hirosue Y., Okita M., et al. (1994) Effects of PP family peptides on feeding and learning behavior in mice. J. Pharmacol. Exp. Ther. 268, 1010–1014.

    PubMed  CAS  Google Scholar 

  • Poucet B. (1993) Spatial cognitive maps in animals: new hypotheses on their structure and neural mechanisms. Psychol. Rev. 100, 163–182.

    Article  PubMed  CAS  Google Scholar 

  • Redrobe J. P., Dumont Y., Fournier A., and Quirion R. (2002). The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology 26, 615–624.

    Article  PubMed  CAS  Google Scholar 

  • Redrobe J. P., Dumont Y., Herzog H., and Quirion R. (2003) Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from NPY Y2 receptor knockout mice. Behav. Brain Res. 141, 251–255.

    Article  PubMed  CAS  Google Scholar 

  • Redrobe J. P., Dumont Y., and Quirion R. (2001) Neuropeptide Y as a potential target for the treatment of depressive illness: Y not? Neurosci. News 4, 61–68.

    Google Scholar 

  • Redrobe J. P., Dumont Y., St-Pierre J. A., and Quirion R. (1999) Multiple receptors for neuropeptide Y in the hippocampus: putative roles in seizures and cognition. Brain Res. 848, 153–166.

    Article  PubMed  CAS  Google Scholar 

  • Sainsbury A., Schwarzer C., Couzens M., Fetissov S., Furtinger S., Jenkins A., et al. (2002). Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knock out mice. Proc. Natl. Acad. Sci. USA 99, 8938–8943.

    Article  PubMed  CAS  Google Scholar 

  • Smith-White M. A., Herzog H., and Potter E. K. (2002) Role of neuropeptide Y Y(2) receptors in modulation of cardiac parasympathetic neurotransmission. Regul. Pept. 103, 105–111.

    Article  PubMed  CAS  Google Scholar 

  • Stanley B. G. and Leibowitz S. F. (1984) Neuropeptide Y: stimulation of feeding and drinking by injection into the paraventricular nucleus. Life Sci. 35, 2635–2642.

    Article  PubMed  CAS  Google Scholar 

  • Steckler T., Drinkenburg W. H. I. M., Sahal A., and Aggleton J. P. (1998) Recognition memory in rats. II. Neuroanatomical substrates. Prog. Neurobiol. 54, 313–332.

    Article  PubMed  CAS  Google Scholar 

  • Stogner K. A. and Holmes P. V. (2000) Neuropeptide-Y exerts antidepressant-like effects in the forced swim test in rats. Eur. J. Pharmacol. 387, R9-R10.

    Article  PubMed  CAS  Google Scholar 

  • Thorsell A., Michalkiewicz M., Dumont Y., Quirion R., Caberlotto L., Rimondini R., et al. (2000) Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression. Proc. Natl. Acad. Sci. USA 97, 12852–12857.

    Article  PubMed  CAS  Google Scholar 

  • Vaucher E., Fluit P., Chisti M. A., Westaway D., Mount H. T. J., and Kar S. (2002a) Object recognition memory and cholinergic parameters in mice expressing human presenilin 1 transgenes. Exp. Neurol. 175, 398–406.

    Article  PubMed  CAS  Google Scholar 

  • Vaucher E., Reymond I., Najaffe R., Kar S., Quirion R., Miller M. M., and Franklin K. B. J. (2002b) Estrogen effects on object memory and cholinergic receptors in young and old female mice. Neurobiol. Aging 23, 87–95.

    Article  PubMed  CAS  Google Scholar 

  • Vezzani A., Sperk G., and Colmers W. F. (1999) Neuropeptide Y: emerging evidence for a functional role in seizure modulation. Trends Neurosci. 22, 25–30.

    Article  PubMed  CAS  Google Scholar 

  • Weiser T., Wieland H. A., and Doods H. N. (2000) Effects of the neuropeptide Y Y2 receptor antagonist BIIE0246 on presynaptic inhibition by neuropeptide Y in rat hippocampal slices. Eur. J. Pharmacol. 404, 133–136.

    Article  PubMed  CAS  Google Scholar 

  • Whishaw I. Q., Cassel J. C., and Jarrard L. E. (1995) Rats with fimbria-fornix lesions display a place response in a swimming pool: a dissociation between getting there and knowing where. J. Neurosci. 15, 5779–5788.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Douglas Hospital Research Centre, Department of Psychiatry, McGill University, H4H 1R3, Montreal, Quebec, Canada

    John Paul Redrobe, Yvan Dumont & Rémi Quirion

  2. Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Sydney, Australia

    Herbert Herzog

Authors
  1. John Paul Redrobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvan Dumont
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Herbert Herzog
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rémi Quirion
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rémi Quirion.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Redrobe, J.P., Dumont, Y., Herzog, H. et al. Characterization of neuropeptide Y, Y2 receptor knockout mice in two animal models of learning and memory processing. J Mol Neurosci 22, 159–166 (2004). https://doi.org/10.1385/JMN:22:3:159

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:22:3:159

Index Entries

Search

Navigation