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

Bazovkina DV, Kondaurova EM, Naumenko VS, Ponimaskin E - Neural Plast. (2015)

Bottom Line: This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of different doses of selective 5-HT2C receptor agonist MK-212 on distance traveled in the open field test in CBA mice. The data are presented as the mean ± SEM (n = 8 per group; ∗p < 0.05, ∗∗∗p < 0.001 versus saline group).
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fig1: Effect of different doses of selective 5-HT2C receptor agonist MK-212 on distance traveled in the open field test in CBA mice. The data are presented as the mean ± SEM (n = 8 per group; ∗p < 0.05, ∗∗∗p < 0.001 versus saline group).

Mentions: The open field test is widely used to evaluate the locomotor activity (total distance traveled in the open field arena) and anxiety-like behavior (time spent in the central part of the arena) in rodents [32, 33]. To analyze the role of 5-HT2C receptor stimulation in modulation of locomotor activity, animals were subjected to the open field test after intraperitoneal injection of increasing concentrations of receptor agonist MK-212 (0.1, 1.0, 2.0, or 4.0 mg/kg). Administration of 5-HT2C receptor agonist induced significant dose-dependent reduction of the distance traveled in the open field in mice of CBA/Lac strain (F4,31 = 6.2, p < 0.001; Figure 1). It is noteworthy that all doses, except for the lowest one (0.1 mg/kg), significantly decreased the path length, while highest MK-212 dose (4.0 mg/kg) produced almost threefold suppression of locomotor activity. For the time spent in the center, one-way ANOVA analysis did not show any effect of 5-HT2C receptor agonist (F4,31 = 1.2, p > 0.05), but the post hoc analysis revealed significant decrease in this index in MK-212-treated (4.0 mg/kg) CBA mice compared to the saline group (p < 0.05; Table 1). MK-212-induced decrease in locomotor activity was 5-HT2C receptor-specific, since the pretreatment of animal with i.p. injection of the highly selective 5-HT2C receptor antagonist RS 102221 (2.0 mg/kg) significantly suppressed MK-212-induced reduction of distance traveled in the open field (F2,22 = 11.4; p < 0.001; Figure 2).


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

Bazovkina DV, Kondaurova EM, Naumenko VS, Ponimaskin E - Neural Plast. (2015)

Effect of different doses of selective 5-HT2C receptor agonist MK-212 on distance traveled in the open field test in CBA mice. The data are presented as the mean ± SEM (n = 8 per group; ∗p < 0.05, ∗∗∗p < 0.001 versus saline group).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4563107&req=5

fig1: Effect of different doses of selective 5-HT2C receptor agonist MK-212 on distance traveled in the open field test in CBA mice. The data are presented as the mean ± SEM (n = 8 per group; ∗p < 0.05, ∗∗∗p < 0.001 versus saline group).
Mentions: The open field test is widely used to evaluate the locomotor activity (total distance traveled in the open field arena) and anxiety-like behavior (time spent in the central part of the arena) in rodents [32, 33]. To analyze the role of 5-HT2C receptor stimulation in modulation of locomotor activity, animals were subjected to the open field test after intraperitoneal injection of increasing concentrations of receptor agonist MK-212 (0.1, 1.0, 2.0, or 4.0 mg/kg). Administration of 5-HT2C receptor agonist induced significant dose-dependent reduction of the distance traveled in the open field in mice of CBA/Lac strain (F4,31 = 6.2, p < 0.001; Figure 1). It is noteworthy that all doses, except for the lowest one (0.1 mg/kg), significantly decreased the path length, while highest MK-212 dose (4.0 mg/kg) produced almost threefold suppression of locomotor activity. For the time spent in the center, one-way ANOVA analysis did not show any effect of 5-HT2C receptor agonist (F4,31 = 1.2, p > 0.05), but the post hoc analysis revealed significant decrease in this index in MK-212-treated (4.0 mg/kg) CBA mice compared to the saline group (p < 0.05; Table 1). MK-212-induced decrease in locomotor activity was 5-HT2C receptor-specific, since the pretreatment of animal with i.p. injection of the highly selective 5-HT2C receptor antagonist RS 102221 (2.0 mg/kg) significantly suppressed MK-212-induced reduction of distance traveled in the open field (F2,22 = 11.4; p < 0.001; Figure 2).

Bottom Line: This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk 630090, Russia.

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.

No MeSH data available.


Related in: MedlinePlus