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Johansson, Inga-Maj
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Publications (10 of 46) Show all publications
Holmberg, E., Sjöstedt, J., Malinina, E., Johansson, M., Turkmen, S., Ragagnin, G., . . . Bäckström, T. (2018). Allopregnanolone involvement in feeding regulation, overeating and obesity. Frontiers in neuroendocrinology (Print), 48, 70-77
Open this publication in new window or tab >>Allopregnanolone involvement in feeding regulation, overeating and obesity
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2018 (English)In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 48, p. 70-77Article, review/survey (Refereed) Published
Abstract [en]

Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA(A) receptors (primarily with alpha 3 and alpha 2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA(A) receptor (with compensatory > 12-, > 5- and > 1.5-fold increases in alpha 4, gamma 2, and alpha 1, alpha 3 subunits), and increases in the alpha 4, beta x, delta receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Allopregnanolone, GABA, GABA(A) receptor, Satiety, Hunger, Obesity, Overeating
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-145173 (URN)10.1016/j.yfrne.2017.07.002 (DOI)000424316800008 ()28694181 (PubMedID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2019-05-06Bibliographically approved
Bixo, M., Johansson, M., Timby, E., Michalski, L. & Bäckström, T. (2018). Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder. Paper presented at 9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY. Journal of neuroendocrinology (Print), 30(2), Article ID e12553.
Open this publication in new window or tab >>Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder
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2018 (English)In: Journal of neuroendocrinology (Print), ISSN 0953-8194, E-ISSN 1365-2826, Vol. 30, no 2, article id e12553Article in journal (Refereed) Published
Abstract [en]

Premenstrual dysphoric disorder (PMDD) afflicts 3%-5% of women of childbearing age, and is characterised by recurrent negative mood symptoms (eg, irritability, depression, anxiety and emotional lability) during the luteal phase of the menstrual cycle. The aetiology of PMDD is unknown, although a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, has been established during the luteal phase. Allopregnanolone is a positive modulator of the GABA(A) receptor: it is sedative in high concentrations but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women. Saccadic eye velocity (SEV) is a measure of GABA(A) receptor sensitivity; in experimental studies of healthy women, i.v. allopregnanolone decreases SEV. Women with PMDD display an altered sensitivity to an i.v. injection of allopregnanolone compared to healthy controls in this model. In functional magnetic resonance imaging (fMRI) studies, women with PMDD react differently to emotional stimuli in contrast to controls. A consistent finding in PMDD patients is increased amygdala reactivity during the luteal phase. Post-mortem studies in humans have revealed that allopregnanolone concentrations vary across different brain regions, although mean levels in the brain also reflect variations in peripheral serum concentrations. The amygdala processes emotions such as anxiety and aggression. This is interesting because allopregnanolone is detected at high concentrations within the region into which marked increases in blood flow are measured with fMRI following progesterone/allopregnanolone administration. Allopregnanolone effects are antagonised by its isomer isoallopregnanolone (UC1010), which significantly reduces negative mood symptoms in women with PMDD when administered s.c. in the premenstrual phase. This was shown in a randomised, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the Daily Rating of Severity of Problems (DRSP): the treatment reduced negative mood scores (P<.005), as well as total DRSP scores (P<.01), compared to placebo in women with PMDD. In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms as a result of its ability to antagonise the allopregnanolone effect on the GABA(A) receptor.

Keywords
GABA, neuroactive steroids, premenstrual dysphoric disorder
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-145601 (URN)10.1111/jne.12553 (DOI)000425521300018 ()
Conference
9th International Meeting on Steroids and Nervous System, FEB 11-15, 2017, Torino, ITALY
Available from: 2018-03-29 Created: 2018-03-29 Last updated: 2018-06-09Bibliographically approved
Johansson, M., Månsson, M., Lins, L.-E., Scharschmidt, B., Doverskog, M. & Bäckström, T. (2018). GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study. Psychopharmacology, 235(5), 1533-1543
Open this publication in new window or tab >>GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study
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2018 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 235, no 5, p. 1533-1543Article in journal (Refereed) Published
Abstract [en]

RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans.

METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs. placebo. GR3027-mediated reversal of allopregnanolone effect on maximal saccadic eye velocity (SEV), and self-rated somnolence was studied in a double-blind, placebo-controlled, three-part cross-over study in which 3 or 30 mg oral GR3027 preceded 0.05 mg/kg of i.v. allopregnanolone.

RESULTS: ]) varied linearly with dose; with dose-dependent accumulation ratios of 1.3-1.6. Allopregnanolone decreased SEV and induced somnolence in most, but not all subjects. By predefined analyses, 30 mg GR3027 significantly inhibited allopregnanolone-induced decrease in SEV (p = 0.03); 3 and 30 mg GR3027 non-significantly inhibited allopregnanolone-induced sedation. By post hoc analyses restricted to subjects with allopregnanolone-induced changes and the time period over which they occurred, GR3027 dose dependently inhibited allopregnanolone-induced decrease in SEV (p = 0.04 at 30 mg, non-significant at 3 mg) and allopregnanolone-induced sedation (p = 0.01/0.05 at 3/30 mg doses).

CONCLUSION: Oral GR3027 mitigates inhibition of brain function induced by allopregnanolone at doses which are clinically well tolerated and associated with linear pharmacokinetics.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Allopregnanolone, Clinical trial, GR3027, Saccadic eye movement, Sedation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-148340 (URN)10.1007/s00213-018-4864-1 (DOI)000431034400018 ()29492615 (PubMedID)
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-10-29Bibliographically approved
Philippens, I. H., Ormel, P. R., Baarends, G., Johansson, M., Remarque, E. J. & Doverskog, M. (2017). Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer's Disease.. Journal of Alzheimer's Disease, 55(1), 101-113
Open this publication in new window or tab >>Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer's Disease.
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2017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 55, no 1, p. 101-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The immune system is increasingly mentioned as a potential target for Alzheimer's disease (AD) treatment.

OBJECTIVE: In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, which has potential as an AD animal model due to its natural cerebral amyloidosis similar to humans.

METHODS: Six adult/aged marmosets (Callithrix jacchus) were intracranial injected with amyloid-beta (Aβ) fibrils at three cortical locations in the right hemisphere. Additionally, in half of the monkeys, lipopolysaccharide (LPS) was co-injected with the Aβ fibrils and injected in the other hemisphere without Aβ fibrils. The other three monkeys received phosphate buffered saline instead of LPS, as a control for the inflammatory state. The effect of inflammation on amyloidopathy was also investigated in an additional monkey that suffered from chronic inflammatory wasting syndrome. Mirror histology sections were analyzed to assess amyloidopathy and immune reaction, and peripheral blood for AD biomarker expression.

RESULTS: All LPS-injected monkeys showed an early AD immune blood cell expression profile on CD95 and CD45RA. Two out of three monkeys injected with Aβ and LPS and the additional monkey, suffering from chronic inflammation, developed plaques. None of the controls, injected with Aβ only, developed any plaques.

CONCLUSION: This study shows the importance of immune modulation on the susceptibility for amyloidosis, a hallmark of AD, which offers new perspectives for disease modifying approaches in AD.

Keywords
Alzheimer’s disease, amyloid, amyloidosis, inflammation, marmoset, microglia, non-human primates, pathology, plaque progression, pro-inflammatory cytokines
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-147600 (URN)10.3233/JAD-160673 (DOI)27662314 (PubMedID)
Available from: 2018-05-09 Created: 2018-05-09 Last updated: 2018-06-09
Johansson, M., Strömberg, J., Ragagnin, G., Doverskog, M. & Bäckström, T. (2016). GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo. Journal of Steroid Biochemistry and Molecular Biology, 160(SI), 98-105
Open this publication in new window or tab >>GABAA receptor modulating steroid antagonists (GAMSA) are functional in vivo
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2016 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 160, no SI, p. 98-105Article in journal (Refereed) Published
Abstract [en]

GABAA receptor modulating steroid antagonists (GAMSA) selectively inhibit neurosteroid-mediated enhancement of GABA-evoked currents at the GABAA receptor. 3α-hydroxy-neurosteroids, notably allopregnanolone and tetrahydrodeoxycorticosterone (THDOC), potentiate GABAA receptor-mediated currents. On the contrary, various 3β-hydroxy-steroids antagonize this positive neurosteroid-mediated modulation. Importantly, GAMSAs are specific antagonists of the positive neurosteroid-modulation of the receptor and do not inhibit GABA-evoked currents. Allopregnanolone and THDOC have both negative and positive actions. Allopregnanolone can impair encoding/consolidation and retrieval of memories. Chronic administration of a physiological allopregnanolone concentration reduces cognition in mice models of Alzheimer's disease. In humans an allopregnanolone challenge impairs episodic memory and in hepatic encephalopathy cognitive deficits are accompanied by increased brain ammonia and allopregnanolone. Hippocampal slices react in vitro to ammonia by allopregnanolone synthesis in CA1 neurons, which blocks long-term potentiation (LTP). Thus, allopregnanolone may impair learning and memory by interfering with hippocampal LTP. Contrary, pharmacological treatment with allopregnanolone can promote neurogenesis and positively influence learning and memory of trace eye-blink conditioning in mice. In rat the GAMSA UC1011 inhibits an allopregnanolone-induced learning impairment and the GAMSA GR3027 restores learning and motor coordination in rats with hepatic encephalopathy. In addition, the GAMSA isoallopregnanolone antagonizes allopregnanolone-induced anesthesia in rats, and in humans it antagonizes allopregnanolone-induced sedation and reductions in saccadic eye velocity. 17PA is also an effective GAMSA in vivo, as it antagonizes allopregnanolone-induced anesthesia and spinal analgesia in rats. In vitro the allopregnanolone/THDOC-increased GABA-mediated GABAA receptor activity is antagonized by isoallopregnanolone, UC1011, GR3027 and 17PA, while the effect of GABA itself is not affected.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Allopregnanolone, Neurosteroids, GABAA receptor, GAMSA, Cognition
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-118532 (URN)10.1016/j.jsbmb.2015.10.019 (DOI)000376840500013 ()26523675 (PubMedID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2018-06-07Bibliographically approved
Bengtsson, S. K., Johansson, M. & Bäckström, T. (2016). Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice. Hormones and Behavior, 78, 160-167
Open this publication in new window or tab >>Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice
2016 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 78, p. 160-167Article in journal (Refereed) Published
Abstract [en]

Chronic stress in various forms increases the risk for cognitive dysfunction, dementia and Alzheimer's disease. While the pathogenesis behind these findings is unknown, growing evidence suggests that chronic increase in neurosteroid levels, such as allopregnanolone, is part of the mechanism. We treated wild-type C57BL/6J mice with allopregnanolone for 5months, using osmotic pumps. This treatment led to moderately increased levels of allopregnanolone, equivalent to that of mild chronic stress. After an interval of no treatment for 1month, female mice showed impaired learning and memory function in the Morris water maze (MWM) in combination with diminished hippocampus weight and increased cerebellum weight, both correlating to MWM performance. Male mice showed a minor reduction in memory function and no differences in brain structure. We conclude that chronic allopregnanolone elevation can lead to cognitive dysfunction and negative brain alterations. We suggest that allopregnanolone could play a key role in the pathogenesis of stress-induced cognitive disturbances and perhaps dementia.

Keywords
Allopregnanolone, Memory and learning, Chronic stress, Mild cognitive impairment, Dementia, Brain tissue weight, GABA, Wild-type mice, C57BL/6J mice
National Category
Neurosciences Other Health Sciences
Identifiers
urn:nbn:se:umu:diva-118533 (URN)10.1016/j.yhbeh.2015.10.010 (DOI)000368962200020 ()26497250 (PubMedID)
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2018-06-07Bibliographically approved
Johansson, M., Agusti, A., Llansola, M., Montoliu, C., Strömberg, J., Malinina, E., . . . Felipo, V. (2015). GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy. American Journal of Physiology - Gastrointestinal and Liver Physiology, 309(5), G400-G409
Open this publication in new window or tab >>GR3027 antagonizes GABA(A) receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy
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2015 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 309, no 5, p. G400-G409Article in journal (Refereed) Published
Abstract [en]

Hepatic encephalopathy (HE) is one of the primary complications of liver cirrhosis. Current treatments for HE, mainly directed to reduction of ammonia levels, are not effective enough because they cannot completely eliminate hyperammonemia and inflammation, which induce the neurological alterations. Studies in animal models show that overactivation of GABA(A) receptors is involved in cognitive and motor impairment in HE and that reducing this activation restores these functions. We have developed a new compound, GR3027, that selectively antagonizes the enhanced activation of GABA(A) receptors by neurosteroids such as allopregnanolone and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC). This work aimed to assess whether GR3027 improves motor incoordination, spatial learning, and circadian rhythms of activity in rats with HE. GR3027 was administered subcutaneously to two main models of HE: rats with chronic hyperammonemia due to ammonia feeding and rats with portacaval shunts (PCS). Motor coordination was assessed in beam walking and spatial learning and memory in the Morris water maze and the radial maze. Circadian rhythms of ambulatory and vertical activity were also assessed. In both hyperammonemic and PCS rats, GR3027 restores motor coordination, spatial memory in the Morris water maze, and spatial learning in the radial maze. GR3027 also partially restores circadian rhythms of ambulatory and vertical activity in PCS rats. GR3027 is a novel approach to treatment of HE that would normalize neurological functions altered because of enhanced GABAergic tone, affording more complete normalization of cognitive and motor function than current treatments for HE.

Place, publisher, year, edition, pages
American Physiological Society, 2015
Keywords
GABA(A) receptors, hyperammonemia, neurosteroids, hepatic encephalopathy
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-109375 (URN)10.1152/ajpgi.00073.2015 (DOI)000360687000012 ()26138462 (PubMedID)
Note

This study was financed by Umecrine Cognition AB

Available from: 2015-09-28 Created: 2015-09-25 Last updated: 2018-06-07Bibliographically approved
Holmberg, E., Johansson, M., Bäckström, T., Löfgren, M. & Haage, D. (2015). Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet. Physiology and Behavior, 140, 1-7
Open this publication in new window or tab >>Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet
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2015 (English)In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 140, p. 1-7Article in journal (Refereed) Published
Abstract [en]

Ingestion of energy rich high fat diets is one of the determining factors associated with the obesity epidemic. Therefore, much can be learned from studies of obesity-related substances given to animals fed a high fat diet.The progesterone metabolite allopregnanolone is a potent positive modulator of the gamma-aminobutyric acid(GABA)A-receptor, and both allopregnanolone and GABA have been implicated in evoking hyperphagia. In this study, food intake and body weight gain were investigated during repeated allopregnanolone exposure. Male Wistar rats were studied when fed chow ad libitum, with chow access for 4h per day or with 45% high fat pellets for 4 h per day. Rats on the high fat diet were separated into obesity prone and obesity resistant individuals.Subcutaneous injections of allopregnanolone were given once daily overfive consecutive days. Repeated exposure to allopregnanolone lead to increased weight gain, significantly so in schedule fed rats on a high fat diet. The increased weight gain was correlated to an increased energy intake. Both obesity resistant and obesityprone rats responded to allopregnanolone with increased weight gain. Obesity resistant rats treated with allopregnanolone increased their energy intake and ate as much as vehicle treated obesity prone rats. Their weight gain was also increased to the level of obesity prone rats injected with just the vehicle carrier oil. Thus, it appears that allopregnanolone may be one of the endogenous factors involved in weight gain, especiallywhen the diet is rich in fat.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Allopregnanolone Neurosteroid Weight gain Food intake Scheduled feeding High fat diet
National Category
Neurosciences Physiology Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-101793 (URN)10.1016/j.physbeh.2014.12.012 (DOI)000349588400001 ()
Available from: 2015-04-13 Created: 2015-04-13 Last updated: 2018-06-07Bibliographically approved
Bäckström, T., Bixo, M., Johansson, M., Nyberg, S., Ossewaarde, L., Ragagnin, G., . . . van Wingen, G. (2014). Allopregnanolone and mood disorders. Progress in Neurobiology, 113, 88-94
Open this publication in new window or tab >>Allopregnanolone and mood disorders
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2014 (English)In: Progress in Neurobiology, ISSN 0301-0082, E-ISSN 1873-5118, Vol. 113, p. 88-94Article in journal (Refereed) Published
Abstract [en]

Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calming anxiolytic effects. Patients with PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and pregnanolone while increased sensitivity to allopregnanolone. This agrees with findings in animals showing a relation between changes in alpha4 and delta subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone. Conclusion: These findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor.

(c) 2013 Elsevier Ltd. All rights reserved.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-87179 (URN)10.1016/j.pneurobio.2013.07.005 (DOI)000331508100007 ()
Available from: 2014-03-31 Created: 2014-03-24 Last updated: 2018-06-08Bibliographically approved
Holmberg, E., Johansson, M., Bäckström, T. & Haage, D. (2014). Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats. Physiological Reports, 2(12), e12190
Open this publication in new window or tab >>Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats
2014 (English)In: Physiological Reports, E-ISSN 2051-817X, Vol. 2, no 12, p. e12190-Article in journal (Refereed) Published
Abstract [en]

Obesity is an increasing problem and identification of the driving forces for overeating of energy-rich food is important. Previous studies show that the stress and sex steroid allopregnanolone has a hyperphagic effect on both bland food and palatable food. If allopregnanolone induces a preference for more palatable or for more energy-rich food is not known. The aim of this study  was to elucidate the influence of allopregnanolone on food preference. Male Wistar rats were subjected to two different food preference tests: a choice between standard chow and cookies (which have a higher energy content and also are more palatable than chow), and a choice between a low caloric sucrose solution and standard chow (which has a higher energy content and is less palatable than sucrose). Food intake was measured for 1 h after acute subcutaneous injections of allopregnanolone. In the choice between cookies and chow allopregnanolone significantly increased only the intake of cookies.When the standard chow was the item present with the highest caloric load, the chow intake was increased and allopregnanolone had no effect on intake of the 10% sucrose solution. The increased energy intakes induced by the high allopregnanolone dose compared to vehicle were very similar in the two tests,120% increase for cookies and 150% increase for chow. It appears that in allopregnanolone-induced hyperphagia, rats choose the food with the highest energy content regardless of its palatability.

Place, publisher, year, edition, pages
Wiley Periodicals Inc., 2014
Keywords
Allopregnanolone, energy need, food intake, neurosteroids GABA
National Category
Neurosciences Physiology
Identifiers
urn:nbn:se:umu:diva-101791 (URN)10.14814/phy2.12190 (DOI)
Available from: 2015-04-13 Created: 2015-04-13 Last updated: 2018-11-28Bibliographically approved
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