GABAA receptors activate fish feeding behaviour via two distinct functional pathways

Abstract

Benzodiazepines, acting through ionotropic receptor of γ-aminobutyric acid (GABAA receptor, GABAR), were shown to modify feeding behaviour and increase appetite in humans and non-human subjects. However, the cellular and molecular mechanisms which 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 GABA-dependent manner. On top of this, orthosteric and allosteric effects were found to be partially competitive, which leads to complex behavioural repercussions of conjoint effects of GABAR ligands.