Apoptotic neurodegeneration and spatial memory are not affected by sedative and anaesthetics doses of ketamine/medetomidine combinations in adult mice

Laboratory Animal Science, Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 02/2012; 108(5):807-14. DOI: 10.1093/bja/aes003
Source: PubMed


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.

1 Follower
11 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegeneration and depression are two common co-morbid conditions, particularly within the aging population. Research has linked neuroinflammation as a major contributing factor to both of these diseases. The key to neuroinflammation effects on neurodegeneration and depression appears to lie within the dysregulation of the control and release of pro- and anti-inflammatory cytokines. This can come from an internal or external insult to the system, or from changes in the individual due to aging that culminate in immune dysregulation. The need to reduce neuroinflammation has led to extensive research into neuroprotectants. We discuss the efficacy found with nicotine, alcohol, resveratrol, curcumin, and ketamine. Our main focus will be on what research tells us about the connections between neuroinflammation, neurodegeneration, and depression, and the hope that neuroprotectants research gives people suffering from neurodegeneration and depression stemming from neuroinflammation. We will conclude by making suggestions for future research in this area.
    Neurotoxicity Research 08/2012; 23(2). DOI:10.1007/s12640-012-9348-1 · 3.54 Impact Factor
  • Source
    [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 · 0.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: α2-Adrenoceptor agonists are used frequently in human and veterinary anesthesia as sedative/analgesic drugs. However, they can impair cognition. Little is known about the concentration-dependent effects of α2-adrenoceptor agonists on synaptic plasticity, the neurophysiological basis of learning and memory. Therefore, we investigated the effects of different concentrations of medetomidine, an α2-adrenoceptor agonist, on basal excitatory synaptic transmission and on 2 forms of synaptic plasticity: paired-pulse facilitation (PPF) and long-term potentiation (LTP). Evoked field excitatory postsynaptic potentials were recorded in Schaffer fibers-CA1 pyramidal cell synapses of mouse hippocampal slices, and the initial field excitatory postsynaptic potentials slope was measured. For basal synaptic transmission and PPF, increasing concentrations of medetomidine (1-200 μM) were applied to each slice. For LTP experiments, individual slices were used for each tested concentration of medetomidine (0.1-0.4 μM), where LTP induction and LTP maintenance were measured. The lower tested concentrations of medetomidine decreased LTP in a concentration-dependent manner, whereas greater concentrations were required to decrease fiber volley amplitude and basal excitatory synaptic transmission. PPF was only affected by the greatest concentration (200 μM). Medetomidine decreased LTP in the mouse hippocampus, in accordance with the ability of medetomidine to induce memory deficits.
    Anesthesia & Analgesia 02/2015; 120(5). DOI:10.1213/ANE.0000000000000636 · 3.47 Impact Factor