Advertisement

Molecular Biology

, Volume 52, Issue 2, pp 212–221 | Cite as

Functional Responses to the Chronic Activation of 5-HT1A Receptors in Mice with Genetic Predisposition to Catalepsy

  • A. S. Tsybko
  • T. V. Ilchibaeva
  • D. V. Bazovkina
  • V. S. Naumenko
Molecular Cell Biology
First Online:
Received:
Accepted:

Abstract

The effects of chronic 5-HT1A receptor activation on the behavior, functional activity of 5-HT1A receptors, and expression of key genes of the brain 5-HT system were studied in mice of the catalepsy-prone CBA strain and the catalepsy-resistant C57BL/6 strain. Chronic treatment with 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) led to a significant decrease in the hypothermic response to acute administration of 8-OH-DPAT in CBA and C57BL/6 mice, which indicates the desensitization of 5-HT1A receptors in both strains. Pretreatment with the 5-HT7 receptor agonist SB 269970 did not affect the hypothermic response to the acute administration of 8-OH-DPAT, which suggests an independent functional response of 5-HT1A receptors. The treatment did not induce any changes in the behavior in the open field paradigm in CBA mice, but significantly increased the total path, the time spent in the center, and the number of rearings in C57BL/6 mice, which indicates the enhancement of locomotor and exploratory activity in C57BL/6 mice. The chronic activation of 5-HT1A receptor downregulated 5-HT1A gene expression, as well as the expression of the gene that encodes tryptophan hydroxylase 2, a key enzyme of 5-HT biosynthesis, in the midbrain and the expression of the gene that encodes the 5-HT2A receptor in the frontal cortex of CBA, but not C57BL/6 mice. The obtained data provide a new evidence on the receptor–gene cross talk in the brain 5-HT system that may underlie the loss of pharmacological efficacy of 5-HT1A receptor agonists. In turn, the loss of the behavioral response and compensatory alterations in key genes of the brain 5- HT system in CBA mice suggests that catalepsy-prone and -resistant genotypes demonstrate different sensibility to the effects of drugs.

Keywords

genetic predisposition to catalepsy chronic 8-OH-DPAT treatment 5-HT1A receptors key genes of the 5-HT system behavior 

Abbreviations

5-HT

serotonin

5-HT1A receptor

serotonin receptor subtype 1A

5-HT2A receptor

serotonin receptor subtype 2A

8-OH-DPAT

8-hydroxy-2-(di-n-propylamino)tetralin

SB269970

(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl) ethyl]pyrrolidine hydrochloride)

rPolII

RNA polymerase II

TPH-2

tryptophan hydroxylase 2

5-HTT

serotonin transporter

RT

reverse transcription

PCR

polymerase chain reaction

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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Popova N.K. 2004. The role of brain serotonin in the expression of genetically determined defensive behavior. Russ. J. Genet. 40 (6), 624–630.CrossRefGoogle Scholar
  2. 2.
    Weder N.D., Muralee S., Penland H., et al. 2008. Catatonia: A review. Ann Clin Psychiatry. 20, 97–107.CrossRefPubMedGoogle Scholar
  3. 3.
    Amir S., Brown Z.W., Amir Z., et al. 1981. Bodypinches induced long lasting cataleptic-like immobility in mice: Behavioral characterization and the effects of naloxone. Life Sci. 10, 1189–1194.CrossRefGoogle Scholar
  4. 4.
    Kulikov A.V., Kozlachkova E.Y., Maslova G.B., et al. 1993. Inheritance of predisposition to catalepsy in mice. Behav. Genet. 23, 379–384.CrossRefPubMedGoogle Scholar
  5. 5.
    Kulikov A.V., Bazovkina D.V., Moisan M.P., et al. 2003. The mapping of the gene of susceptibility to catalepsy in mice using polymorphic microsatellite markers. Dokl. Biol. Sci. 393, 531–534.CrossRefPubMedGoogle Scholar
  6. 6.
    Kulikov A.V. 2004. Hereditary catalepsy: genetic and molecular mechanisms of catalepsy in mice. Russ. J. Genetics. 40, 631–637.CrossRefGoogle Scholar
  7. 7.
    Kulikov A.V., Bazovkina D.V., Kondaurova E.M., et al. 2008. Genetic structure of hereditary catalepsy in mice. Genes Brain Behav. 7, 506–512.CrossRefPubMedGoogle Scholar
  8. 8.
    Neal-Beliveau B.S., Joyce J.N., Lucki I. 1993. Serotonergetic involvement in haloperidol-induced catalepsy. Exp. Ther. 265, 207–217.Google Scholar
  9. 9.
    Wadenberg M.L. 1996. Serotonergic mechanisms in neuroleptic-induced catalepsy in the rat. Neurosci. Biobehav. Rev. 20, 325–339.CrossRefPubMedGoogle Scholar
  10. 10.
    Prinssen E.P., Colpaert F.C., Koek W. 2002. 5-HT1A receptor activation and anti-cataleptic effects: Highefficacy agonists maximally inhibit haloperidolinduced catalepsy. Eur. J. Pharmacol. 453, 217–221.CrossRefPubMedGoogle Scholar
  11. 11.
    Ohno Y., Shimizu S., Imaki J. 2009. Effects of tandospirone, a 5-HT1A agonistic anxiolytic agent, on haloperidol-induced catalepsy and forebrain Fos expression in mice. J. Pharmacol. Sci. 109, 593–599.CrossRefPubMedGoogle Scholar
  12. 12.
    Newman-Tancredi A. 2010. The importance of 5-HT1A receptor agonism in antipsychotic drug action: Rationale and perspectives. Curr. Opin. Investig. 11, 802–812.Google Scholar
  13. 13.
    Iderberg H., McCreary A.C., Varney M.A., et al. 2015. NLX-112, a novel 5-HT1A receptor agonist for the treatment of l-DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat. Exp. Neurol. 271, 335–350.CrossRefPubMedGoogle Scholar
  14. 14.
    Kulikov A.V., Kolpakov V.G., Maslova G.B., et al. 1994. Effect of selective 5-HT1A agonists and 5-HT2 antagonists on inherited catalepsy in rats. Psychopharmacology. 114, 172–174.CrossRefPubMedGoogle Scholar
  15. 15.
    Popova N.K., Kulikov A.V. 1995. On the role of brain serotonin in expression of genetic predisposition to catalepsy in animal models. Am. J. Med. Genet. Neuropsychiatric Gene). 60, 214–220.CrossRefGoogle Scholar
  16. 16.
    Popova N.K., Kulikov A.V., Avgustinovich D.F., et al. 1994. Influence of brain 5-HT1A serotonin receptors in the regulation of inherited catalepsy. Bull. Exp. Biol. Med. 118, 633–635.Google Scholar
  17. 17.
    Bazovkina D.V., Terenina E.E., Kulikov A.V. 2010. Effect of selective agonist of serotonin 5-HT1A receptors on defensive behavior in mice with different predisposition to catalepsy. Bull. Exp. Biol. Med. 150, 225–228.CrossRefPubMedGoogle Scholar
  18. 18.
    Kondaurova E.M., Bazovkina D.V., Kulikov A.V., et al. 2006. Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice. Genes Brain Behav. 5, 596–601.CrossRefPubMedGoogle Scholar
  19. 19.
    Bazovkina D.V., Kulikova A.V., Kondaurova E.M., et al. 2005. Selection for the predisposition to catalepsy enhances depressive-like traits in mice. Russ. J. Genetics. 41, 1002–1007.CrossRefGoogle Scholar
  20. 20.
    Tikhonova M.A., Kulikov A.V., Bazovkina D.V., et al. 2013. Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response. Behav. Brain Res. 243, 53–60.CrossRefPubMedGoogle Scholar
  21. 21.
    Tikhonova M.A., Al’perina E.L., Tolstikova T.G., et al. 2009. Effects of chronic fluoxetine treatment on catalepsy and immune response in mice genetically predisposed to freezing reaction: The role of 5-HT1A and 5-HT2A receptors and tph2 and SERT genes. Zh. Vyssh. Nerv. Deiat. im. I. P. Pavlova. 59, 237–244.PubMedGoogle Scholar
  22. 22.
    Naumenko V.S., Kondaurova E.M., Bazovkina D.V., et al. 2012. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 214, 59–67.CrossRefPubMedGoogle Scholar
  23. 23.
    Albert P.R., François B.L. 2010. Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy. Front. Neurosci. 4, 35. doi 10.3389/fnins.2010.00035PubMedPubMedCentralGoogle Scholar
  24. 24.
    Popova N.K., Naumenko V.S. 2013. 5-HT1A receptor as a key player in the brain 5-HT system. Rev. Neurosci. 24, 191–204.PubMedGoogle Scholar
  25. 25.
    Celada P., Bortolozzi A., Artigas F. 2013. Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research. CNS Drugs. 27, 703–716.CrossRefPubMedGoogle Scholar
  26. 26.
    Watson J., Collin L., Ho M., et al. 2000. 5-HT(1A) receptor agonist–antagonist binding affinity difference as a measure of intrinsic activity in recombinant and native tissue systems. Br. J. Pharmacol. 130, 1108–1114.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Assie M.B., Koek W. 2000. [(3)H]-8-OH-DPAT binding in the rat brain raphe area: Involvement of 5-HT(1A) and non-5-HT(1A) receptors. Br. J. Pharmacol. 130, 1348–1352.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kulikov A.V., Tikhonova M.A., Kulikov V.A. 2008. Automated measurement of spatial preference in the open field test with transmitted lighting. J. Neurosci. Meth. 170, 345–351.CrossRefGoogle Scholar
  29. 29.
    Overstreet D.H. Rezvani A.H., Knapp D.J., et al. 1996. Further selection of rat lines differing in 5-HT-1A receptor sensitivity: Behavioral and functional correlates. Psychiat. Genet. 6, 107–117.CrossRefGoogle Scholar
  30. 30.
    Barnes N.M., Sharp T. 1999. A review of central 5-HT receptors and their function. Neuropharmacology. 38, 1083–1152.CrossRefPubMedGoogle Scholar
  31. 31.
    Slotnick B.M., Leonard C.M. 1975. A Stereotaxic Atlas of the Albino Mouse Forebrain. Rockville, MD: U.S. Dept. of Health, Education and Welfare.Google Scholar
  32. 32.
    Naumenko V.S., Kulikov A.V. 2006. Quantitative assay of 5-HT(1A) serotonin receptor gene expression in the brain. Mol. Biol. (Moscow). 40, 30–36.CrossRefGoogle Scholar
  33. 33.
    Brookshire B.R., Jones S.R. 2009. Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice. Pharmacol. Biochem. Behav. 94, 194–203.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Piñeyro G., Blier P. 1999. Autoregulation of serotonin neurons: Role in antidepressant drug action. Pharmacol. Rev. 51, 533–591.PubMedGoogle Scholar
  35. 35.
    Popova N.K., Naumenko V.S., Tibeikina M.A., et al. 2009. Serotonin transporter, 5-HT1A receptor, and behavior in DBA/2J mice in comparison with four inbred mouse strains. J. Neurosci. Res. 87, 3649–3657.CrossRefPubMedGoogle Scholar
  36. 36.
    Martin K.F., Phillips I., Hearson M., et al. 1992. Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants. Br. J. Pharmacol. 107, 15–21.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Blier P., Seletti B., Gilbert F., et al. 2002. Serotonin 1A receptor activation and hypothermia in humans: Lack of evidence for a presynaptic mediation. Neuropsychopharmacology. 27, 301–308.CrossRefPubMedGoogle Scholar
  38. 38.
    Popova N.K., Naumenko V.S., Cybko A.S., et al. 2010. Receptor-genes cross-talk: Effect of chronic 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin treatment on the expression of key genes in brain serotonin system and on behavior. Neuroscience. 169, 229–235.CrossRefPubMedGoogle Scholar
  39. 39.
    Naumenko V., Kondaurova E.M., Popova N.K. 2011. On the role of brain 5-HT7 receptor in the mechanism of hypothermia: Comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor. Neuropharmacology. 61, 1360–1365.CrossRefPubMedGoogle Scholar
  40. 40.
    De Vry J., Schreiber R., Melon C., et al. 2004. 5-HT1A receptors are differentially involved in the anxiolyticand antidepressant-like effects of 8-OH-DPAT and fluoxetine in the rat. Eur. Neuropsychopharmacology. 14, 487–495.CrossRefGoogle Scholar
  41. 41.
    Bert B., Fink H., Hörtnagl H., et al. 2006. Mice overexpressing the 5-HT(1A) receptor in cortex and dentate gyrus display exaggerated locomotor and hypothermic response to 8-OH-DPAT. Behav. Brain Res. 167, 328–341.CrossRefPubMedGoogle Scholar
  42. 42.
    Naumenko V.S., Bazovkina D.V., Kondaurova E.M., et al. 2010. The role of 5-HT2A receptor and 5-HT2A/5-HT1A receptor interaction in the suppression of catalepsy. Genes Brain Behav. 9, 519–524.PubMedGoogle Scholar
  43. 43.
    Mintun M.A., Sheline Y.I., Moerlein S.M., et al. 2004. Decreased hippocampal 5-HT2A receptorbinding in major depressive disorder: In vivo measurement with [18F]altanserin positron emission tomography. Biol. Psychiatry. 55, 217–224.CrossRefPubMedGoogle Scholar
  44. 44.
    Naumenko V.S., Bazovkina D.V., Kondaurova E.M. 2015. On the functional cross-talk between brain 5-HT1A and 5-HT2A receptors. Zh. Vyssh. Nerv. Deiat. im. I. P. Pavlova. 65, 240–247.PubMedGoogle Scholar
  45. 45.
    Pineyro G., Blier P. 1999. Autoregulation of serotonin neurons: Role in antidepressant drug action. Pharmacol. Rev. 51, 533–591.PubMedGoogle Scholar
  46. 46.
    Blier P., de Montigny C. 1994. Current advances and trends in the treatment of depression. Trends Pharmacol. Sci. 15, 220–226.CrossRefPubMedGoogle Scholar
  47. 47.
    Goppelt-Struebe M., Hahn A., Stroebel M., et al. 1999. Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen-activated protein kinases and Ca2/calmodulin-dependent kinase. Biochem. J. 339, 329–334.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Simon A.R., Severgnini M., Takahashi S., et al. 2005. 5-HT induction of c-fos gene expression requires reactive oxygen species and Rac1 and Ras GTPases. Cell Biochem. Biophys. 42, 263–276.CrossRefPubMedGoogle Scholar
  49. 49.
    Naumenko V.S., Popova N.K., Lacivita E., et al. 2014. Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders. CNS Neurosci. Ther. 20, 582–590.CrossRefPubMedGoogle Scholar
  50. 50.
    Popova N.K., Ponimaskin E.G., Naumenko V.S. 2015. Cross-talk between 5-HT1A and 5-HT7 receptors: Role in the autoregulation of the brain serotonin system and in mechanism of antidepressants action. Ross. Fiziol. Zh. im. I.M. Sechenova. 101, 1270–1278.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • A. S. Tsybko
    • 1
  • T. V. Ilchibaeva
    • 1
  • D. V. Bazovkina
    • 1
  • V. S. Naumenko
    • 1
  1. 1.Institute of Cytology and GeneticsSiberian Branch of the Russian Academy of SciencesNovosibirskRussia

Personalised recommendations

Cite article

Buy options