Apoptotic neurodegeneration and spatial memory are not affected by sedative and anaesthetics doses of ketamine/medetomidine combinations in adult mice
ABSTRACT Ketamine is increasingly popular in clinical practice and its combination with α(2)-agonists can provide good anaesthetic stability. Little is known about the effects of this combination in the brain. Therefore, we investigated the effects of different concentrations of ketamine combined with medetomidine on cognition and its potential apoptotic neurodegenerative effect in adult mice.
Seventy-eight C57BL/6 adult mice were divided into six different groups (saline solution, 1 mg kg(-1) medetomidine, 25 mg kg(-1) ketamine+1 mg kg(-1) medetomidine, 75 mg kg(-1) ketamine+1 mg kg(-1) medetomidine, 25 mg kg(-1) ketamine, and 75 mg kg(-1) ketamine). Eight animals per group were tested in the T-maze, vertical pole, and open-field test. Five animals per group were used for histopathological [haematoxylin and eosin (HE) staining] and immunohistochemical analyses [caspase-3 activation and expression of neurotrophin brain-derived neurotrophic factor (BDNF)]. Cells showing clear HE staining and positive immunoreactions for caspase-3 and BDNF in the retrosplenial cortex, visual cortex, pyramidal cell layer of the cornu Ammonis 1 and cornu Ammonis 3 areas of the hippocampus, and in the granular layer of the dentate gyrus were counted.
There were no differences between groups regarding the number of dead cells and cells showing positive immunoreactions in the different areas of the brain studied. Similarly, no differences were detected in the number of trials to complete the T-maze task. Nevertheless, α(2)-agonist decreased hyperlocomotion caused by ketamine in the open field.
Neither apoptotic neurodegeneration nor alterations in spatial memory were observed with different concentrations of ketamine combined with medetomidine in adult mice.
SourceAvailable from: Rodrigo A Cunha[Show abstract] [Hide abstract]
ABSTRACT: Ketamine is frequently used to induce analgesia or anesthesia in laboratory animals, but its effects on learning and memory are poorly characterized. Long-term potentiation (LTP) is considered a cellular mechanism for learning and memory. Ketamine administration immediately abolishes hippocampal LTP in vivo, but whether this effect persists is not known. The authors administered one of two doses of ketamine to adult male C57BL/6 mice and measured LTP in hippocampal slices from the mice 24 h later. Neither LTP induction nor LTP maintenance differed significantly in mice that were administered ketamine compared with mice that were administered saline. The findings suggest that a single intraperitoneal dose of ketamine does not persistently alter LTP in adult male mice.Lab Animal 09/2014; 43(10):353-7. DOI:10.1038/laban.571 · 0.81 Impact Factor
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