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
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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

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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

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