The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task

Abstract

We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA), serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (B max) of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippocampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phenotropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1 receptors. Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil increased the density of receptors by 16% and 25%, respectively. Phenotropil considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results demonstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical mechanisms of the anti-amnestic effects of phenotropil.

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

References

  1. 1.

    Akhapkina, V.N., Fenotropil. Sb. St., 2007, pp. 6–14.

  2. 2.

    Filippova, S.Yu., Aleshina, N.V., and Stepanov, V.P., Fenotropil. Sb. St., 2007, pp. 84–87.

  3. 3.

    Kovalev, G.I., Akhapkina, V.I., Abaimov, D.A., and Firstova, Yu.Yu., Atmosfera. Nervnye Bolezni, 2007, no. 4, pp. 22–26.

  4. 4.

    Kovalev, G.I. Doctorate (Med.) Dissertation [in Russian], Moscow: NII farmakologii im. V.V. Zakusova, 1993.

  5. 5.

    Zhao, X., Kuryatov, A., Lindstrom, J., Yah, J., and Narahashi, T., Mol. Pharmacol., 2001, vol. 59(4), pp. 674–683.

    PubMed  CAS  Google Scholar 

  6. 6.

    Firstova, Yu.Yu., Cand. Sci. (Biol.) Dissertation [in Russian], Moscow: NII farmakologii im. V.V. Zakusova, 2008.

  7. 7.

    Kovalev, G.I. and Prikhozhan, A.V., Farmakologiya nootropov. Eksperimental’noe i klinicheskoe izuchenie. Val’dman A.V., Voronina T.A., Eds., Moscow, 1989, pp. 99–104.

  8. 8.

    Kovalev, G., Kudrin, V., Zharikov, S., Pogorelov, V., Bogdanov, M., and Guinetdinov, R., Abstr. of Meeting Dopamine-92, Italy, 1992, p. 29.

  9. 9.

    Copani, A., Genezzani, A.A., Aleppo, G., Casadona, G., and Canonico, P.L., J. Neurochem., 1992, vol. 58, pp. 1199–1204.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Narahashi, T., Moriguchi, S., Zhao, X., Marszalec, W., and Yeh, J.Z., Biol. Pharm. Bull., 2004, vol. 27(11), pp. 1701–1706.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Voronina, T.A. and Ostrovskaya, R.U., in Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv (Manual on Experimental (Preclinical) Studies of New Pharmacological Compounds), Moscow, 2000, pp. 153–158.

  12. 12.

    Glowinski, J. and Iversen, L., J. Neurochem., 1966, vol. 13(8), pp. 655–669.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Alexander, S.P., Mathie, A., and Peters, J.A., Guide to Receptors and Channels. BJP, 2006, vol. 147, no. 3, p. 146.

    Google Scholar 

  14. 14.

    Sun, W., Ginovart, N., Ko, F., Seeman, P., and Kapur, S., Mol. Pharmacol., 2003, vol. 63(2), pp. 456–462.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Romano, C. and Goldstein, A., Science, 1980, vol. 210, pp. 647–650.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Zhou, L.M., Gu, Z.Q., Costa, A.M., Yamada, K.A., and Manssone, P.E., J. Pharmacol. Exp. Ther., 1997, vol. 280, pp. 422–427.

    PubMed  CAS  Google Scholar 

  17. 17.

    Andersen, P.H., Gronvald, F.C., and Jansen, J.A., Life Sci., 1985, vol. 37, pp. 1971–1983.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Levesque, D., Diaz, J., Pilon, C., Martres, M.P., Giros, B., Souil, E., Schott, D., Morgat, J.L., Schwartz, J.C., and Sokoloff, P., Proc. Natl. Acad. Sci. USA, 1992, vol. 89, pp. 8155–8159.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Cohen, S.A. and Mller, W.E., Pharmacol., 1993, vol. 47, pp. 217–222.

    Article  CAS  Google Scholar 

  20. 20.

    Pilch, H. and Mller, W.E., Psychopharmacol., 1988, vol. 94, pp. 74–78.

    Article  CAS  Google Scholar 

  21. 21.

    Pepeu, G. and Sprignoli, G., Prog. Neuropsychopharmacol. Biol. Psychiatry, 1989, vol. 13, pp. 77–88.

    Article  Google Scholar 

  22. 22.

    Pepeu, G., Sprignoli, G., and Goivannini, M.G., Pharmacopsychiatry, 1999, vol. 22(2), pp. 116–119.

    Article  Google Scholar 

  23. 23.

    Yamada, K., Tanaka, T., and Mamiya, T.I., Brit. J. Pharmacol., 1999, vol. 126(1), pp. 235–244.

    Article  CAS  Google Scholar 

  24. 24.

    Scheuer, K., Rostock, A., and Bartsh, R., Pharmacopsychiatry, 1999, vol. 32, pp. 10–16.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Memo, M., Missale, C., Trivelli, L., and Spano, P.F., Eur. J. Pharmacol., 1988, vol. 149(3), pp. 367–370.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Stewart, M.G., Kabai, P., Harrison, E., Steele, R.J., Kossut, M., and Csillag, A., Neuroscience, 1996, vol. 70(1), pp. 7–14.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Nitta, A., Katono, Y., Itoh, A., Hasegawa, T., and Nabeshima, T., Pharmacol. Biochem. Behav., 1994, vol. 49(4), pp. 8072–8080.

    Article  Google Scholar 

  28. 28.

    Dubrovina, N.I., Neurosci. Behav. Physiol., 2006, vol. 36, no. 6, pp. 679–684.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Aramakis, V.B. and Metherate, R., J. Neurosci., 1998, vol. 18, pp. 257–263.

    Google Scholar 

  30. 30.

    Gould, Th.J. and Lewis, M.C., Learn. Mem, 2005, vol. 12, pp. 389–398.

    PubMed  Article  Google Scholar 

  31. 31.

    Lloyd, G.K. and Williams, M., J. Pharmacol. Exp. Ther., 2000, vol. 292(2), pp. 461–467.

    PubMed  CAS  Google Scholar 

  32. 32.

    Mohler, H., Fritschy, J.M., and Rudolph, U., J. Pharmacol. Exp. Ther., 2002, vol. 300(1), pp. 2–8.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yu. Yu. Firstova.

Additional information

Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Firstova, Y.Y., Abaimov, D.A., Kapitsa, I.G. et al. The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task. Neurochem. J. 5, 115–125 (2011). https://doi.org/10.1134/S1819712411020048

Download citation

Keywords

  • phenotropil
  • nootropic drugs
  • scopolamine
  • PAT
  • dopamine
  • serotonin
  • acetylcholine
  • glutamate
  • benzodiazepines
  • striatum
  • frontral cortex
  • hippocampus