Organotypic Cultures as Tools for Testing Neuroactive Drugs - Link Between In-Vitro and In-Vivo Experiments
General anaesthesia is based on the modulation of neurotransmitter receptors and other conductances located on neurons in diverse brain regions, including cerebral cortex and spinal cord. It is well known that different components of general anaesthesia, e.g. hypnosis and immobility, are produced by the depression of neuronal activity in distinct brain regions. The ventral horn of the spinal cord is an important structure for the induction of immobility. Thus, the potentially immobilizing effects of a newly designed drug can be estimated from its depressant effect on neuronal network activity in cultured spinal slices. A drug's sedative and hypnotic potential can be examined in cortical cultures. Combined with genetically engineered mice, this approach can point to receptor subtypes most relevant to the drug's intended net effect and in return can help in the design of more selective drugs. In conclusion, the use of organotypic cultures permits predictions of neuroactive properties of newly designed drugs on an intermediate level, and should therefore open up avenues for a more creative and economic drug development process.
Keywords: GABA(A) receptor; GABAergic interneurons; Metabotropic GABAB receptors; Organotypic cultures; Pyramidal neurons; allosteric binding site; amnestic; amygdala; anaesthetics; antiepileptic; benzodiazepines; bicuculline; brain stem; cerebellum; cholinergic neurons; cortex; dopaminergic cells; electroencenphalogram (EEG); extrasynaptic sites; hippocampus; human embryo kidney (HEK); immobilizing effects; inhibitory postsynaptic currents; ionotropic GABAA receptors; local field potential (LFP); mivacurium; neocortex; neurotransmitters; phosphorylation; potassium channels; propofol; rocuronium; spinal cord; synchronizing; thalamic axon
Document Type: Research Article
Publication date: 01 December 2010
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