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

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.

Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors

“…Scale bar is 10 µm. A summary graph showing average of emission ratio (FRET/CFP) in each condition n=number of cells [number of animals], Male; saline = 74 ( Ali et al, 2020 ) and ketamine = 55 ( Akillioglu et al, 2012 ), Female; saline = 61 ( Ali et al, 2020 ) and ketamine = 130 ( Akillioglu and Karadepe, 2021 ), *p<0.05 and **p<0.01, unpaired two-tailed student t-test. A scale bar indicates 25 μm.…”

“…Both the open field test and tail suspension test have long been used to determine animals’ anxiety- and depression-like behaviors, respectively, in rodents ( Seibenhener and Wooten, 2015 ; Ueno et al, 2022 ). Specifically, the open field test has been widely used to measure the ketamine effects on anxiety-like behavior in rodents ( Guarraci et al, 2018 ; Pitsikas et al, 2019 ; Shin et al, 2019 ; Akillioglu and Karadepe, 2021 ; Yang et al, 2022 ; Acevedo et al, 2023 ). We thus measured locomotor activity and anxiety-like behavior using the open field test as carried out previously ( Shou et al, 2019 ).…”

Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults

“…NMDAR blockade during the developmental period has previously been associated with persistent anxiety in adulthood ( Wedzony et al, 2008 ). In the EPM maze study, Akillioglu and Karadepe demonstrated that single and repetitive doses of 10 and 20 mg/kg on the 7th post-natal day increased anxiety-like behavior in adulthood ( Akillioglu and Karadepe, 2021 ). Onaolapo's study ( Onaolapo et al, 2019 ) showed that subchronic ketamine administration increased time spent in the open arm of the EPM at all doses studied (7, 15, or 30 mg/kg per day for 8 weeks), indicating that ketamine may have an anxiolytic effect.…”