Effects Of Using Ketamine Combined With Penehyclidine Hydrochloride In Neonatal Rats On Developments Of Learning And Memory,synaptophysin Expression And Synaptic Ultrastructure In The Region Of Hippocampal CA3

Objective To observe the effects of using ketamine combined with penehyclidine hydrochloride in neonatal rats on developments of learning and memory,synaptophysin expression and synaptic ultrastructure in the region of hippocampal CA3.Methods One hundred seven-day-old Sprague-Dawly rats were randomly divided into four groups,( namely group K, group P, group PK, group NS)and intraperitoneally injected with 50mg/Kg of ketamine(group K),2mg/Kg of penehyclidine hydrochloride(group P), 50mg/Kg of ketamine plus 2mg/Kg of penehyclidine hydrochloride(group PK) or normal saline(group NS) respectively. The performances of every rat in neurological behavior (included with Open field,Novel objects recognition and Morris water maze) were tested at 14 days(phaseⅠ) and 21 days(phaseⅡ) after treatment.At the time points of 24-hr,14-day and 28-day after the medication, the immunhistochemical method was used for detecting the expression of synaptophysin in the region of hippocampal CA3, and synaptic numerical densities and synaptic ultrastructure also in the region of hippocampal CA3 were measured and observed under electron microscope.Results①Morris water maze tests at phase I, the escape latency in group K increased obviously compared to that in group NS or group P,and it increased further in group PK;oppositely,the preference index and the spatial probing time for previous platform in group K and group PK decreased remarkably compared to that in group NS or group P,especially for that in group PK.About searching strategies, there was no obvious difference for the indices of edge,trend,random strategies among four groups. The average percentage of straight strategy in group PK was significantly lower than that in group NS. Morris water maze tests at phaseⅡ, group PK performed worst, followed by group K, group NS and group P performed best.②There was no significant difference for the results in Open field tests among each group.③Novel object recognition tests at phase I, group NS and group P were the best, followed by group K, group PK performed worst. Results got in phaseⅡhad no significant difference among each group .④Compared with group NS and group P, the expression of synaptophysin in group K decreased significantly 24 hrs and 14 days after administration, and group PK was lower than group K. Up to 28 days after administration, the synaptophysin expression increased in all of the four groups and there were no significant differences between groups.⑤Compared with group NS and group P, group K showed significant decreases in synaptic numeric density,postsynaptic density thicknes and synaptic cleft 24 hrs and 14 days after administration, and group PK was lower than group K. Up to 28 days after administration, the synaptic ultrastructure optimized in all of the four groups and there were no significant differences between groups.There was no any significant difference for all indices at every time point mentioned above compared between group P and group NS. Conclusions The using of Ketamine together with penehyclidine hydrochloride or alone in neonatal rats both hindered the development of learning and memory,synaptophysin expression,synaptic numerical densities and the optimization of the synaptic ultrastructure in the region of hippocampal CA3, but the former did more significantly than the latter.However,the adverse effects mentioned aboved may diminished by learning,training and increasing of age, so that no difference was found for the adult rats in different groups.The administration of penehyclidine hydrochloride alone had no visibly disadvantageous effect on all the indices detected in this research.