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The additive effect of allopregnanolone on ghrelin's orexigenic effect in rats

Löfgren, Magnus ; Holmberg, Ellinor ; Bäckström, Torbjörn ; Egecioglu, Emil LU and Dickson, Suzanne L. (2019) In Neuropeptides 76.
Abstract

The progesterone metabolite, allopregnanolone (AlloP), is a GABAA receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABAA-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected... (More)

The progesterone metabolite, allopregnanolone (AlloP), is a GABAA receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABAA-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected intravenously with AlloP and/or ghrelin, alone or in combination. The intake of the standard chow was greater after AlloP 1 mg/kg together with ghrelin 30 μg/kg than with 30 μg/kg ghrelin alone. Food intake was also increased for the combined treatment of AlloP 0.5 mg/kg + ghrelin 10 μg/kg, AlloP 1 mg/kg + ghrelin 10 μg/kg, and AlloP 0.5 mg/kg + ghrelin 30 μg/kg. There was no significant difference in food intake between the two ghrelin doses or between the two doses of AlloP and the vehicle. In electrophysiological studies, physiologically relevant concentrations of AlloP prolonged the current decay time of spontaneous inhibitory post-synaptic current of dissociated cells of the ARC and PVN. We conclude that AlloP enhances the hyperphagic effect of ghrelin, findings of potential relevance for the hyperphagia associated with the luteal phase of the reproductive cycle.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Allopregnanolone, ARC, Brexanolone, Food intake, GABA-receptor, Ghrelin, Patch-clamp, PVN
in
Neuropeptides
volume
76
article number
101937
publisher
Elsevier
external identifiers
  • pmid:31253440
  • scopus:85067673899
ISSN
0143-4179
DOI
10.1016/j.npep.2019.101937
language
English
LU publication?
yes
id
957131c7-5da4-4ef9-89f1-411e13214787
date added to LUP
2019-07-05 13:28:42
date last changed
2020-01-13 11:17:21
@article{957131c7-5da4-4ef9-89f1-411e13214787,
  abstract     = {<p>The progesterone metabolite, allopregnanolone (AlloP), is a GABA<sub>A</sub> receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABA<sub>A</sub>-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected intravenously with AlloP and/or ghrelin, alone or in combination. The intake of the standard chow was greater after AlloP 1 mg/kg together with ghrelin 30 μg/kg than with 30 μg/kg ghrelin alone. Food intake was also increased for the combined treatment of AlloP 0.5 mg/kg + ghrelin 10 μg/kg, AlloP 1 mg/kg + ghrelin 10 μg/kg, and AlloP 0.5 mg/kg + ghrelin 30 μg/kg. There was no significant difference in food intake between the two ghrelin doses or between the two doses of AlloP and the vehicle. In electrophysiological studies, physiologically relevant concentrations of AlloP prolonged the current decay time of spontaneous inhibitory post-synaptic current of dissociated cells of the ARC and PVN. We conclude that AlloP enhances the hyperphagic effect of ghrelin, findings of potential relevance for the hyperphagia associated with the luteal phase of the reproductive cycle.</p>},
  author       = {Löfgren, Magnus and Holmberg, Ellinor and Bäckström, Torbjörn and Egecioglu, Emil and Dickson, Suzanne L.},
  issn         = {0143-4179},
  language     = {eng},
  month        = {06},
  publisher    = {Elsevier},
  series       = {Neuropeptides},
  title        = {The additive effect of allopregnanolone on ghrelin's orexigenic effect in rats},
  url          = {http://dx.doi.org/10.1016/j.npep.2019.101937},
  doi          = {10.1016/j.npep.2019.101937},
  volume       = {76},
  year         = {2019},
}