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Neuroscience and Behavioral Physiology

, Volume 43, Issue 5, pp 650–655 | Cite as

Peptidergic Modulation of Synaptic Activity in the Hippocampus

  • V. G. SkrebitskiiEmail author
  • R. V. Kondratenko
  • I. S. Povarov
  • V. I. Derevyagin
Article

We present here results from studies of the physiological mechanisms of action of two neuropeptides widely used in clinical practice as nootropes and anxiolytics: Noopept, a peptide analog of piracetam and, Selank, a synthetic analog of the peptide tuftsin. Patch-clamp studies on hippocampal slices addressed the modulation of spontaneous inhibitory ion currents in pyramidal neurons on exposure to study neuropeptides. The main effect of both substances consisted of an increase in the frequency of spontaneous inhibitory postsynaptic currents (IPSC) in pyramidal cells of the radial layer of field CA1, evidently due to an increase in the discharge frequency of inhibitory interneurons terminating on these cells (demonstrated only for Noopept). The consequence of the increase in IPSC frequency in pyramidal neurons is strengthening of the inhibitory control of limbic structures by the hippocampus, which in turn appears to underlie the anxiolytic effects of both agents. The mechanisms of their nootropic actions will be addressed in future studies.

Keywords

Noopept Selank nootropes anxiolytics hippocampus patch clamping IPSC inhibitory interneurons 

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References

  1. 1.
    F. Yu. Belozertsev, I. I. Kozlovskii, T. P. Semenova, and M. M. Kozlovskaya, “Effects of the neuropeptide Selank on acquisition of an adaptive spatial visual orientation skill in rats with impaired mnestic function,” Zh. Psikhofarm. Biol. Narkol., 9, 2591–2597 (2009).Google Scholar
  2. 2.
    T. A. Gudasheva, R. U. Ostrovskaya, F. V. Maksimova, et al., “Possible structural-functional relationships between piracetam and vasopressin,” Khim.-Farm. Zh., 3, 271–275 (1988).Google Scholar
  3. 3.
    T. A. Gudasheva, R. U. Ostrovskaya, S. S. Trofimov, et al., “Peptide analogs of piracetam as ligands of presumptive nootropic receptors,” Khim.-Farm. Zh., 11, 1322–1328 (1985).Google Scholar
  4. 4.
    A. A. Zozulya, G. G. Neznamov, T. S. Syunyakov, et al., “Efficacy and mechanisms of action of the new peptide anxiolytic Selank in the treatment of generalized anxiety disorder and neurasthenia,” Zh. Nevrol. Psikhiat. im. Korsakova, 13, 201–210 (2008).Google Scholar
  5. 5.
    A. N. Chepkova, N. A. Kiapai, N. V. Doreuli, et al., “Effects of the amide pyroglutamylasparagine on the plastic properties of synaptic transmission in the hippocampus,” Byull. Eksperim. Biol. Med., 7, 68–71 (2003).Google Scholar
  6. 6.
    L. J. Bertoglio, S. R. Joka, and F. S. Guimaraes, “Further evidence that anxiety and memory are regionally dissociated within the hippocampus,” Behav. Brain Res., 175, 183–188 (2006).PubMedCrossRefGoogle Scholar
  7. 7.
    A. N. Chepkova, P. French, D. De Wied, et al., “Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4–8),” Brain Res., 701, No. 1–2, 255–266 (1995).PubMedCrossRefGoogle Scholar
  8. 8.
    D. De Wied, “Neuropeptides in learning and memory processes,” Behav. Brain Res., 83, No. 1–2, 83–90 (1997).PubMedCrossRefGoogle Scholar
  9. 9.
    P. Y. Deng, J. E. Porter, H. S. Shin, and S. Lei, “Thyrotropin-releasing hormone increases GABA release in rat hippocampus,” J. Physiol., 577, 497–511 (2006).PubMedCrossRefGoogle Scholar
  10. 10.
    C. Giurgea, “Pharmacology of integrative activity of the brain. Attempt at nootropic concept in psychopharmacology,” Actual Pharmacol. (Paris), 25, 115–116 (1972).Google Scholar
  11. 11.
    T. A. Gudasheva, S. S. Boyko, R. U. Ostrovskaya, et al., “The major metabolite of dipeptide piracetam analogue GVD-111 in right brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine,” Eur. Drug. Metab. Pharmacokinet., 22, 245–252 (1997).CrossRefGoogle Scholar
  12. 12.
    T. A. Gudasheva, M. A. Konstantinopol’skii, R. U. Ostrovskaya, and S. B. Seredenin, “Anxiolytic activity of endogenous nootropic dipeptide cycloprolylglycine in elevated plus-maze test,” Bull. Exp. Biol. Med., 131, 464–466 (2001).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Hughes (ed.), Centrally Acting Peptides, University Part Press (1978).Google Scholar
  14. 14.
    R. Kondratenko, V. I. Derevyagin, and V. G. Skrebitsky, “Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells,” Neurosci. Lett., 476, 70–73 (2010).PubMedCrossRefGoogle Scholar
  15. 15.
    M. B. Kozhemiakin, A. Draguhn, and V. G. Skrebitsky, “Layer-specific potentiation of evoked IPSCs in rat hippocampal CA1 pyramidal cells by lanthanum,” Brain Res. Bull., 64, 97–101 (2004).PubMedCrossRefGoogle Scholar
  16. 16.
    G. Lynch and C. M. Gall, “Ampakines and the threefold path to cognitive enhancement,” Trends Neurosci., 29, 554–672 (2006).PubMedCrossRefGoogle Scholar
  17. 17.
    K. K. Miller, A. Hoffer, K. R. Svoboda, and C. R. Lupica, “Cholecystokinin increases GABA release by inhibiting a resting K+ conductance in hippocampal interneurons,” J. Neurosci., 17, 4994–5003 (1997).PubMedGoogle Scholar
  18. 18.
    H. Mohler and J. G. Richards, “Benzodiazepine receptors in the central nervous system,” in: The Benzodiazepines: From Molecular Biology to Clinical Practice, E. Costa (ed.), Raven Press, New York (1983).Google Scholar
  19. 19.
    R. U. Ostrovksya, M. A. Gruden, N. A. Bobkova, et al., “The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer’s disease model,” J. Psychopharmacol., 21, 611–619 (2007).CrossRefGoogle Scholar
  20. 20.
    B. Winblad, “Piracetam: a review of pharmacological properties and clinical uses,” CNS Drug Review, 11, 169–182 (2005).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • V. G. Skrebitskii
    • 1
    Email author
  • R. V. Kondratenko
    • 1
  • I. S. Povarov
    • 1
  • V. I. Derevyagin
    • 1
  1. 1.Scientific Center for NeurologyRussian Academy of Medical SciencesMoscowRussia

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