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. 2021 Feb 28;19(1):93-103.
doi: 10.9758/cpn.2021.19.1.93.

Effect Neonatal Ketamine Treatment on Exploratory and Anxiety-like Behaviours in Adulthood

Kübra Akillioglu  1 , Mustafa Karadepe  2
Affiliations

Effect Neonatal Ketamine Treatment on Exploratory and Anxiety-like Behaviours in Adulthood

Kübra Akillioglu et al. Clin Psychopharmacol Neurosci. .

Abstract

Objective: In this study, we evaluated the effect of neonatal ketamine exposure on anxiety-like and exploratory behaviours in adult the Balb/c and C57BL/6 strains of mice which anxiety responses are different.

Methods: Ketamine was administered at two different doses single dose (10, 20 mg/kg, 0.1 ml/10 g body weight, intraperitoneally) and repeated doses (10, 20 mg/kg every 240 minutes; thrice times) on the 7th postnatal day to male Balb/c and C57BL/6 mice. In adulthood, open-field (OF) and elevated plus maze (EPM) apparatuses were used to evaluate exploratory and anxiety-like behaviour.

Results: In the C57BL/6 mice, the 20 mg/kg single dose decreased open-arm time and total-arm entries in EPM and increased time of central latency and decreased distance travelled in OF. Both the 10 and 20 mg/kg repetitive doses increased time of central latency and decreased time spent in the centre, frequency of rearing and centre crossing in OF and decreased open-arm time, total-arm entries, number of open-arm entries in EPM. The 20 mg/kg repetitive dose decreased number of head dipping behaviours in EPM. In the Balb/c mice, both the single and repetitive 10-20 mg/kg doses had no significant effect on anxiety-like and exploratory behaviours.

Conclusion: There were no significant differences in anxiety-like and exploratory behaviour in different strains by the single 10 mg/kg dose. However, in the C57BL/6 mice, both the single and repetitive 20 mg/kg doses and the 10 mg/kg repetitive dose increased anxiety-like behaviour and decreased exploratory behaviour in EPM and OF. In conclusion, hereditary factors may be effective on the effect of neonatal ketamine treatment on anxiety-like and exploratory behaviour.

Keywords: Anxiety; BALB C mice; C57BL mice; Exploratory behavior; Ketamine.

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Conflict of interest statement

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Timeline of the experimental procedures. OF, open field test; EPM, elevated plus maze; KET, ketamine; PD, post-natal day.
Fig. 2
Fig. 2
The time spent in the centre of the open field in the adult mice exposed to a single dose of ketamine in their neonatal periods. The data are expressed as mean ± standard error. KET, ketamine. ***p < 0.001 in comparison to the Balb/c control (saline) group, ## p < 0.01, ### p < 0.001 in comparison to the C57BL/6 control (saline) group. The statistical analysis included a two-way ANOVA followed by Tukey’s HSD test.
Fig. 3
Fig. 3
Distance travelled in the open-field test (cm) in the adult mice subjected to a single neonatal dose of ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. # p < 0.05 in comparison to the C57BL/6 control (saline) group. Statistical analysis included a two-way ANOVA followed by Tukey’s HSD test.
Fig. 4
Fig. 4
The time spent in the centre of the open field in the adult mice subjected to repetitive doses neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. **p < 0.01 in comparison to the Balb/c control (saline) group, ## p < 0.01 in comparison to the C57BL/6 control (saline) group. Statistical analysis included a two-way ANOVA followed by Tukey’s HSD test.
Fig. 5
Fig. 5
The distance travelled in the open-field test (cm) in the adult mice subjected to the repetitive doses of neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. **p < 0.01 in comparison to the Balb/c control (saline) group. Mann−Whitney Utest.
Fig. 6
Fig. 6
The time spent in the open arms of the elevated plus maze (sec) in the adult mice subjected to a single dose of neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. **p < 0.01 in comparison to the Balb/c control (saline) group, # p < 0.05 in comparison to the C57BL/6 control (saline) group. Mann−Whitney Utest.
Fig. 7
Fig. 7
The time spent in the closed arms (sec) in the adult mice subjected to a single dose of neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. **p < 0.01 in comparison to the Balb/c control (saline) group, # p < 0.05 in comparison to the C57BL/6 control (saline) group. Statistical analysis included a two-way ANOVA followed by Tukey’s HSD test.
Fig. 8
Fig. 8
The time spent in the open arms (sec) of the elevated plus maze in the adult mice subjected to repetitive doses of neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. **p < 0.01 in comparison to the Balb/c control (saline) group, # p < 0.05 in comparison to the C57BL/6 control (saline) group. Mann−Whitney Utest.
Fig. 9
Fig. 9
Time spent in the closed arms of the elevated plus maze in the adult mice subjected to repetitive doses of neonatal ketamine exposure. The data are expressed as mean ± standard error. KET, ketamine. *p < 0.05 in comparison to the Balb/c control (saline) group, # p < 0.05 in comparison to the C57BL/6 control (saline) group. Statistical analysis included a two-way ANOVA followed by Tukey’s HSD test.
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References

    1. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351–354. doi: 10.1016/s0006-3223(99)00230-9. - DOI - PubMed
    1. Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801–811. doi: 10.1038/mp.2017.255. - DOI - PMC - PubMed
    1. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51:199–214. doi: 10.1001/archpsyc.1994.03950030035004. - DOI - PubMed
    1. Silvestre JS, Nadal R, Pallarés M, Ferré N. Acute effects of ketamine in the holeboard, the elevated-plus maze, and the social interaction test in Wistar rats. Depress Anxiety. 1997;5:29–33. - PubMed
    1. Pitychoutis PM, Thelen C, Sens J, Mauch J, Pandit R. Sex differences in the neurochemical and behavioral antidepressant-like effects of ketamine in mice. Biol Psychiatry. 2016;79(9 Suppl):154s.