ABSTRACT
Benzodiazepines, acting through ionotropic receptors of γ-aminobutyric acid (GABAA receptors, GABAR), have been shown to modify feeding behaviour and increase appetite in humans and non-human subjects. However, the cellular and molecular mechanisms that underlie connected short-term behavioural fluctuations are still unclear. In the present study, we used Carassius gibelio (Prussian carp) as a model organism to research the impact of scantily explored benzodiazepine phenazepam (PNZ) on feeding behaviour and the related molecular mechanisms of PNZ action at single-cell and single-receptor levels. We found that the feeding activity of C. gibelio is under control of GABARs via two distinct mechanisms: orthosteric (triggered by GABA binding site) and allosteric (triggered by benzodiazepine binding site). PNZ displayed clear stimulatory effects on both mechanisms in a GABA-dependent manner. In addition, orthosteric and allosteric effects were found to be partially competitive, which leads to complex behavioural repercussions of conjoint effects of GABAR ligands.
FOOTNOTES
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: S. Snigirov, S. Sylantyev; Methodology: S. Sylantyev; Validation: S. Snigirov; Formal analysis: S. Sylantyev; Investigation: S. Snigirov, S. Sylantyev; Data curation: S. Snigirov, S. Sylantyev; Writing - original draft: S. Sylantyev; Writing - review & editing: S. Snigirov, S. Sylantyev; Supervision: S. Sylantyev; Project administration: S. Sylantyev; Funding acquisition: S. Sylantyev.
Funding
This work was supported by the Rosetrees Trust (research grant A1066), a University of Edinburgh Chancellor's Fellow Start-up grant, and a Wellcome Trust – University of Edinburgh Institutional Strategic Support Fund Award to S. Sylantyev. Deposited in PMC for release after 6 months.
- Received September 14, 2017.
- Accepted November 27, 2017.
- © 2018. Published by The Company of Biologists Ltd
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