GABAA receptors activate fish feeding behaviour via two distinct functional pathways

Abstract

Benzodiazepines, acting through ionotropic receptors of γ-aminobutyric acid (GABA 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 (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 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.

Rare Earth Elements Lanthanum and Praseodymium Adversely Affect Neural and Cardiovascular Development in Zebrafish (Danio rerio)

“…GABA is the major inhibitory neurotransmitter in the brain . GABA signaling blockage has been widely demonstrated to activate behavior in vertebrates, including zebrafish. , In comparison, serotonin signaling has more complex and multifaceted functions . Serotonin receptor agonists were reported to increase swimming behavior, such as locomotor activity, and cooperative behavior in fish. , Thus, our observations at the neurotransmitter level are consistent with the altered swimming behavior and, therefore, suggest a reasonable mechanistic explanation at the molecular level.…”

“…37 GABA signaling blockage has been widely demonstrated to activate behavior in vertebrates, including zebrafish. 41,42 In comparison, serotonin signaling has more complex and multifaceted functions. 43 Serotonin receptor agonists were reported to increase swimming behavior, such as locomotor activity, and cooperative behavior in fish.…”

Development and Molecular Investigation into the Effects of Carbamazepine Exposure in the Zebrafish (Danio rerio)

“…Nevertheless, our data suggest that CBZ exposure may result in an imbalance between excitatory and inhibitory neurotransmission based upon altered receptor expression as well as biosynthetic enzymes. Taken together, changes in brain GABA are expected to contribute to the persistence of deficiencies in locomotor activity reported in studies using zebrafish [43][44][45].…”

“…The Gabra1 receptor subunit is localized at synapses in mature neurons and is structurally critical for the formation of ionic channels [47]. Recent studies have shown that GABA A receptor expression is altered by environmental contaminants, such as phenazepam, which can also lead to abnormal regulation of feeding behavior [44]. Moreover, abat and gad1b, two enzymes involved in regulating glutamate-GABA metabolic pathways, were also inhibited by CBZ exposure.…”

Reliability of behavioral test with fish: How neurotransmitters may exert neuromodulatory effects and alter the biological responses to neuroactive agents

“…The alterations previously mentioned, may bring adverse consequences to the species involved, but also to the population due to changes in locomotor activity, which may result in alterations of feeding, sexual and social behavior (Snigirov and Sylantyev, 2018).…”