Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

Neural Plast. 2015:2015:846589. doi: 10.1155/2015/846589. Epub 2015 Aug 26.

Abstract

In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamines / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Genotype
  • Head Movements / drug effects
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Motor Activity / genetics*
  • Pyrazines / pharmacology
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptor, Serotonin, 5-HT2C / drug effects
  • Receptor, Serotonin, 5-HT2C / genetics*
  • Serotonin 5-HT2 Receptor Agonists / pharmacology
  • Species Specificity
  • Spiro Compounds / pharmacology
  • Sulfonamides / pharmacology

Substances

  • 5-hydroxytryptamine2C receptor, mouse
  • 8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione
  • Amphetamines
  • Pyrazines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • Spiro Compounds
  • Sulfonamides
  • 6-chloro-2-(1-piperazinyl)pyrazine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine