The evaluation of the effect of deksmedetomidine administrationbefore the use of ketamine in repeated sedations i̇n neonatal rats on ketamine-related learning, memory and electrophysiological changes in the preadolescent period

Objective: The aim of this study is to investigate the learning, memory and electrophysiological changes occuring in the pre-adolescent period with Deksmedetomidine prior to Ketamine applications in the neonatal period. Materials and Methods: 75 newborn male and female Wistar rats were included in the study and randomized into five groups; Control group (no injection), Sham group (administiration of repeated doses of saline (0.9% isotonic) on postnatal days 7, 9, 11), DEX group (administiration of 20 mcg/kg, i.p. Deksmedetomidine in repeated doses on postnatal days 7, 9, 11), KET group (administiration of 75 mg/kg i.p Ketamine in repeated doses on postnatal days 7, 9, 11) and DEX+KET group (administiration of 20 mcg/kg, i.p Deksmedetomidine in repeated doses on postnatal days 7, 9, 11 and administiration of 75 mg/kg i.p Ketamine after 5 minutes). 50% O2 was applied to all groups. Morris water tank (MWT) tests started on the 45th postnatal day in all groups. Probe trial was performed on the 50th postnatal day, followed by open field test (OFT) and elevated plus maze test (EPM test). Long Term Potentiation (LTP) records were taken under anesthesia on the 52nd postnatal day and decapitated under anesthesia. Results: In behavioral experiments performed after repeated doses of Deksmedetomidine, Ketamine and Deksmedetomidine-Ketamine injection to newborn rats, significant differences were found between groups in the MWT test, OFT and EPM test. It was found that the DEX group had similar results to the Control and Sham groups in all tests. In MWT tests, it was observed that rats in the KET and DEX+KET groups spent less time in the target quadrant. In OFT, it was observed that the total distance traveled and the ratio of time spent in the inner quadrant/outer quadrant of the rats in the KET and DEX+KET groups decreased. Additionally, it was observed that the average speed of the KET group decreased, while the average speed of the DEX+KET group increased. In EPM test, it was found that the time spent in the open arm and the time spent in the open arm index decreased, and the time spent in the closed arm increased in the KET and DEX+KET groups. When the changes in LTP recordings compared to the values taken in the baseline recordings were examined, it was found that the changes in EPSP slopes and PS amplitudes in the DEX group were similar to the Control and Sham groups. It was found that the change in EPSP slopes and PS amplitude was significantly reduced in the KET and DEX+KET groups compared to the Sham group. (EPSP values; Control (152.01±14.91), Sham (168.01±18.99), DEX (150.89±8.77), KET (107.88±1.51) and DEX+KET (107.79±2, 72).PS values: Control (140.13±14.66), Sham (152.48±9.75), DEX (136.20±11.54), KET (119.10±2.67) and DEX+KET (111.82± 3.35)) Conclusions: With this study, we found that the application of Ketamine in the developing rat brain and in repeated doses causes learning, memory, locomotor activity and anxiety-like behavioral disorders in the preadolescent period. We have found by electrophysiological recordings that long-term memory is impaired and neurotoxic. No adverse effects of deksmedetomidine were observed on the developing rat brain when administered alone or in repeated doses. However, we have shown through behavioral experiments and electrophysiological recordings that Deksmedetomidine cannot positively change Ketamine-related damage.