Abstract
The field of neuropharmacology has not yet achieved a full understanding of how the brain transitions between states of consciousness and drug-induced unconsciousness, or anesthesia. Many small molecules are used to alter human consciousness, but the repertoire of underlying molecular targets, and thereby the genes, are incompletely understood. Here we describe a robust larval zebrafish model of anesthetic action, from sedation to general anesthesia. We use loss of movement under three different conditions, spontaneous movement, electrical stimulation or a tap, as a surrogate for sedation and general anesthesia, respectively. Using these behavioral patterns, we find that larval zebrafish respond to inhalational and IV anesthetics at concentrations similar to mammals. Additionally, known sedative drugs cause loss of spontaneous larval movement but not to the tap response. This robust, highly tractable vertebrate model can be used in the detection of genes and neural substrates involved in the transition from consciousness to unconsciousness.
Highlights
The field of neuropharmacology has not yet achieved a full understanding of how the brain transitions between states of consciousness and drug-induced unconsciousness, or anesthesia
We saw no loss in movement to tap stimulus (TAP) up to 150 μM dexmedetomidine (Fig. 4b), but we found that there was an 80% decrease in movement to electrical stimulation (ELEC) (Fig. 4a, purple) at 150 μM dexmedetomidine
We show that a vertebrate model system, the larval zebrafish, can provide a simple, robust, quantitative model of drug-induced behaviors that should be reproduced in other laboratories
Summary
The field of neuropharmacology has not yet achieved a full understanding of how the brain transitions between states of consciousness and drug-induced unconsciousness, or anesthesia. We describe a robust larval zebrafish model of anesthetic action, from sedation to general anesthesia. We use loss of movement under three different conditions, spontaneous movement, electrical stimulation or a tap, as a surrogate for sedation and general anesthesia, respectively. Using these behavioral patterns, we find that larval zebrafish respond to inhalational and IV anesthetics at concentrations similar to mammals. Known sedative drugs cause loss of spontaneous larval movement but not to the tap response This robust, highly tractable vertebrate model can be used in the detection of genes and neural substrates involved in the transition from consciousness to unconsciousness. Loss of spontaneous movement (SPONT) models light sedation, movement in response to electrical stimulation (ELEC) models deep sedation and movement in response to a tap stimulus (TAP) models general a nesthesia[22]
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