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Lundgren, Per
Publications (10 of 14) Show all publications
Kask, K., Bäckström, T., Lundgren, P. & Sundström Poromaa, I. (2009). Allopregnanolone has no effect on startle response and prepulse inhibition of startle response in patients with premenstrual dysphoric disorder or healthy controls. Pharmacology, Biochemistry and Behavior, 92(4), 608-613
Open this publication in new window or tab >>Allopregnanolone has no effect on startle response and prepulse inhibition of startle response in patients with premenstrual dysphoric disorder or healthy controls
2009 (English)In: Pharmacology, Biochemistry and Behavior, ISSN 0091-3057, E-ISSN 1873-5177, Vol. 92, no 4, p. 608-613Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Allopregnanolone is an endogenous neuroactive steroid which, through the binding to the GABA(A) receptor, enhances inhibitory neurotransmission and exerts anxiolytic, sedative and antiepileptic effects. Following acute administration, allopregnanolone reliably acts as an anxiolytic compound. The primary aim of this study was to investigate if allopregnanolone, administered to healthy women and women with premenstrual dysphoric disorder (PMDD), would have an anxiolytic effect, expressed as a decreased startle response. MATERIALS AND METHODS: Sixteen PMDD patients and twelve healthy controls completed the study. The participants were scheduled for the startle tests twice in the luteal phase. During the test sessions an intravenous allopregnanolone and placebo bolus injection was administered in double-blinded, randomized order at intervals of 48 h. Following the allopregnanolone/placebo injections startle response and prepulse inhibition of startle response (PPI) were assessed by electromyography. RESULTS: Following the intravenous allopregnanolone administration the serum concentrations of allopregnanolone increased to 50-70 nmol/l, corresponding to levels that are seen during pregnancy. The obtained serum concentrations of allopregnanolone were significantly lower in PMDD patients than among the healthy controls, p<0.05. The allopregnanolone injection resulted in significant increases of self-rated sedation in both groups, p<0.01. Allopregnanolone did not induce any changes in startle response or prepulse inhibition of startle response in comparison to placebo. No differences in allopregnanolone-induced changes in startle response or PPI could be detected between PMDD patients and controls subjects. CONCLUSION: Startle response and PPI were unaffected by acute intravenous administration of allopregnanolone in PMDD patients and healthy controls.

Keyword
Allopregnanolone; Premenstrual dysphoric disorder; Startle response; Prepulse inhibition
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:umu:diva-36806 (URN)10.1016/j.pbb.2009.02.014 (DOI)19268499 (PubMedID)
Available from: 2010-10-12 Created: 2010-10-12 Last updated: 2017-12-12Bibliographically approved
Strömberg, J., Lundgren, P., Taube, M., Bäckström, T., Wang, M. & Haage, D. (2009). The effect of the neuroactive steroid 5β-pregnane-3β, 20(R)-diol on the time course of GABA evoked currents is different to that of pregnenolone sulphate. European Journal of Pharmacology, 605(1-3), 78-86
Open this publication in new window or tab >>The effect of the neuroactive steroid 5β-pregnane-3β, 20(R)-diol on the time course of GABA evoked currents is different to that of pregnenolone sulphate
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2009 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 605, no 1-3, p. 78-86Article in journal (Refereed) Published
Abstract [en]

The endogenous progesterone metabolite allopregnanolone has a number of properties including anesthetic, sedative, antiepileptic, anxiolytic, impaired memory function and negative mood symptoms. Allopregnanolone is a potent positive GABA(A) receptor function modulators. In contrast, 3beta-hydroxy-steroids (3beta-steroids) usually modulate the GABA(A) receptor negatively. They have attracted some interest for their possible use as therapeutic agents that could counteract the negative symptoms induced by allopregnanolone. Two hypotheses for the action of 3beta-steroids have been proposed: 1) 3beta-steroids act in a similar way to pregnenolone sulphate, which non-competitively reduces GABA(A) receptor activity. 2) 3beta-steroids specifically antagonize the effect of allopregnanolone. We have therefore tried to clarify this issue by comparing the effect of pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol on the GABA-evoked currents by the patch clamp technique on neurons from the medial preoptic nucleus. Both pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol increase the desensitization rate of the current response evoked by a 2 s GABA application. However, their effects on other parameters of the GABA evoked currents differed in degree and sometimes even in direction. The actions of pregnenolone sulphate and 5beta-pregnane-3beta, 20(R)-diol were not altered in the presence of allopregnanolone, which indicates that they do not directly interact with allopregnanolone. In addition, when 5beta-pregnane-3beta, 20(R)-diol was tested on spontaneous inhibitory postsynaptic currents (sIPSCs), it dramatically reduced the allopregnanolone-induced prolongation of the decay time constant but it had no effect on the decay under control conditions. In conclusion, the effect of 5beta-pregnane-3beta, 20(R)-diol on GABA-evoked currents is different to that of pregnenolone sulphate in medial preoptic nucleus neurons.

Keyword
Patch clamp; sIPSCs; Tau decay; Desensitization; (Rat)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:umu:diva-36809 (URN)10.1016/j.ejphar.2008.12.038 (DOI)19168059 (PubMedID)
Available from: 2010-10-12 Created: 2010-10-12 Last updated: 2017-12-12Bibliographically approved
Wang, M.-D., Borra, V. B., Strömberg, J., Lundgren, P., Haage, D. & Bäckström, T. (2008). Neurosteroids 3beta, 20 (R/S)-pregnandiols decrease offset rate of the GABA-site activation at the recombinant GABA(A) receptor.. Eur J Pharmacol, 586(1-3), 67-73
Open this publication in new window or tab >>Neurosteroids 3beta, 20 (R/S)-pregnandiols decrease offset rate of the GABA-site activation at the recombinant GABA(A) receptor.
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2008 (English)In: Eur J Pharmacol, ISSN 0014-2999, Vol. 586, no 1-3, p. 67-73Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-9998 (URN)18374329 (PubMedID)
Available from: 2008-06-04 Created: 2008-06-04 Last updated: 2011-04-12Bibliographically approved
Birzniece, V., Bäckström, T., Johansson, I.-M., Lindblad, C., Lundgren, P., Löfgren, M., . . . Zhu, D. (2006). Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.. Brain Research Reviews, 51(2), 212-239
Open this publication in new window or tab >>Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.
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2006 (English)In: Brain Research Reviews, ISSN 0165-0173, E-ISSN 1872-6321, Vol. 51, no 2, p. 212-239Article in journal (Refereed) Published
Keyword
Animals, Brain/drug effects/*metabolism/physiopathology, Cognition/drug effects, Cognition Disorders/chemically induced/*metabolism/physiopathology, Gonadal Steroid Hormones/adverse effects/*metabolism, Humans, Learning/drug effects, Neural Pathways/drug effects/metabolism/physiopathology, Receptors; GABA-A/metabolism, Serotonin/*metabolism, gamma-Aminobutyric Acid/*metabolism
Identifiers
urn:nbn:se:umu:diva-15313 (URN)doi:10.1016/j.brainresrev.2005.11.001 (DOI)16368148 (PubMedID)
Available from: 2008-01-04 Created: 2008-01-04 Last updated: 2017-12-14Bibliographically approved
Strömberg, J., Haage, D., Taube, M., Bäckström, T. & Lundgren, P. (2006). Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor. Neuroscience, 143(1), 73-81
Open this publication in new window or tab >>Neurosteroid modulation of allopregnanolone and GABA effect on the GABA-A receptor
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2006 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 143, no 1, p. 73-81Article in journal (Refereed) Published
Keyword
Analysis of Variance, Animals, Brain/cytology, Cells; Cultured, Chloride Channels/drug effects/physiology, Chlorides/metabolism, Dose-Response Relationship; Drug, Drug Interactions, Male, Membrane Potentials/drug effects/physiology/radiation effects, Neurons/*drug effects/physiology, Patch-Clamp Techniques/methods, Pregnanolone/*pharmacology, Rats, Rats; Wistar, Receptors; GABA-A/*metabolism, Steroids/*pharmacology, gamma-Aminobutyric Acid/*pharmacology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-10000 (URN)10.1016/j.neuroscience.2006.07.031 (DOI)16938407 (PubMedID)
Available from: 2008-06-04 Created: 2008-06-04 Last updated: 2017-12-14Bibliographically approved
Löfgren, M., Johansson, I.-M., Meyerson, B., Lundgren, P. & Bäckström, T. (2006). Progesterone withdrawal effects in the open field test can be predicted by elevated plus maze performance. Hormones and Behavior, 50(2), 208-215
Open this publication in new window or tab >>Progesterone withdrawal effects in the open field test can be predicted by elevated plus maze performance
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2006 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 50, no 2, p. 208-215Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone (3alpha-hydroxy-5alpha-pregnane-20-one) is a ring-A-reduced metabolite of progesterone, which is naturally produced during the luteal phase of the menstrual cycle, during pregnancy and by stressful events. The steroid hormone inhibits neural functions through increased chloride ion flux through the GABAA receptor. The effects and subsequent withdrawal symptoms are similar to those caused by alcohol, benzodiazepines and barbiturates. This study examined the withdrawal effects of progesterone with regards to the influence of individual baseline exploration and risk taking. Rats were tested on the elevated plus maze (EPM) before hormonal treatment, in order to evaluate differences in risk taking and exploration of open and elevated areas. Treatment consisted of ten consecutive once a day progesterone or vehicle s.c. injections. On the last day of treatment, estradiol was injected in addition to progesterone, followed by a 24-h withdrawal before testing in the open field test (OF). Progesterone-treated rats showed a withdrawal effect of open area avoidance in the OF. The vehicle-treated control rats showed strong correlations between the EPM and OF parameters. This relationship was not found for the progesterone group at withdrawal. Rats with greater numbers of open arm entrance in the EPM pretest showed an increased sensitivity to progesterone withdrawal (PWD) compared to rats with low exploration and risk taking. The results indicate that the effects of PWD relate to individual exploration and risk taking. Furthermore, the possible analogy of PWD and PMS/PMDD in relation to individual traits is discussed.

Keyword
Animals, Anxiety/*psychology, Behavior; Animal/drug effects/*physiology, Exploratory Behavior/physiology, Male, Motor Activity/physiology, Progesterone/*adverse effects, Rats, Rats; Wistar, Receptors; GABA-A/drug effects, Risk-Taking, Substance Withdrawal Syndrome/*psychology
Identifiers
urn:nbn:se:umu:diva-16926 (URN)10.1016/j.yhbeh.2006.03.002 (DOI)16677649 (PubMedID)
Available from: 2007-10-22 Created: 2007-10-22 Last updated: 2017-12-14Bibliographically approved
Strömberg, J., Bäckström, T. & Lundgren, P. (2005). Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor. European Journal of Neuroscience, 21(8), 2083-2088
Open this publication in new window or tab >>Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the gamma-aminobutyric acid-A receptor
2005 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 21, no 8, p. 2083-2088Article in journal (Other academic) Published
Keyword
Animals, Cerebral Cortex/*cytology, Chlorides/metabolism, Desoxycorticosterone/*analogs & derivatives/pharmacology, Dose-Response Relationship; Drug, Drug Interactions, Glucocorticoids/*metabolism/*pharmacology, Male, Neurons/*cytology/drug effects/metabolism, Pregnanolone/pharmacology, Rats, Rats; Wistar, Receptors; GABA-A/*metabolism, Synaptosomes/*drug effects, gamma-Aminobutyric Acid/pharmacology
Identifiers
urn:nbn:se:umu:diva-9999 (URN)10.1111/j.1460-9568.2005.04047.x (DOI)15869504 (PubMedID)
Available from: 2008-06-04 Created: 2008-06-04 Last updated: 2017-12-14Bibliographically approved
Turkmen, S., Lundgren, P., Birzniece, V., Zingmark, E., Bäckström, T. & Johansson, I.-M. (2004). 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.. European Journal of Neuroscience, 20(6), 1604-1612
Open this publication in new window or tab >>3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.
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2004 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 20, no 6, p. 1604-1612Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is a progesterone metabolite and GABA-A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3beta-hydroxypregnane steroids antagonize allopregnanolone-induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) as a blocker of allopregnanolone-induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2-hydroxypropyl-beta-cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone-injected group on day 6. Day 3-6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone-injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3-6), compared to the allopregnanolone-injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 micro m GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA-A receptor reduce the negative allopregnanolone effect on learning in the water maze.

Keyword
Analysis of Variance, Animals, Behavior; Animal, Cerebral Cortex/drug effects/metabolism, Chlorides/metabolism, Chromatography; High Pressure Liquid/methods, Dose-Response Relationship; Drug, Drug Synergism, GABA Antagonists/*therapeutic use, GABA Modulators/blood/*toxicity, Hippocampus/drug effects/metabolism, Learning Disorders/chemically induced/*drug therapy, Male, Maze Learning/drug effects, Pregnanediol/pharmacology/*therapeutic use, Pregnanolone/blood/pharmacology/therapeutic use/*toxicity, Radioimmunoassay/methods, Rats, Rats; Wistar, Reaction Time/drug effects, Statistics; Nonparametric, Time Factors, gamma-Aminobutyric Acid/physiology
Identifiers
urn:nbn:se:umu:diva-16941 (URN)10.1111/j.1460-9568.2004.03610.x (DOI)15355327 (PubMedID)
Available from: 2007-10-22 Created: 2007-10-22 Last updated: 2017-12-14Bibliographically approved
Lundgren, P., Strömberg, J., Bäckström, T. & Wang, M. (2003). Allopregnanolone-stimulated GABA-mediated chloride ion flux is inhibited by 3beta-hydroxy-5alpha-pregnane-20-one (isoallopregnanolone). Brain Research, 982(1), 45-53
Open this publication in new window or tab >>Allopregnanolone-stimulated GABA-mediated chloride ion flux is inhibited by 3beta-hydroxy-5alpha-pregnane-20-one (isoallopregnanolone)
2003 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 982, no 1, p. 45-53Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-2183 (URN)10.1016/S0006-8993(03)02939-1 (DOI)12915239 (PubMedID)
Available from: 2007-03-27 Created: 2007-03-27 Last updated: 2017-12-14Bibliographically approved
Gunnarsson, D., Nordberg, G., Lundgren, P. & Selstam, G. (2003). Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats. Toxicology, 183((1-3)), 57-63
Open this publication in new window or tab >>Cadmium-induced decrement of the LH receptor expression and cAMP levels in the testis of rats
2003 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 183, no (1-3), p. 57-63Article in journal (Refereed) Published
Abstract [en]

Cadmium (Cd) is a widespread environmental pollutant, characterized by its ability to affect various organs. Adverse effect of Cd on the testis including decreased testosterone production are well-known phenomena, but the cellular events explaining these effects have not yet been established. In the present study the initial steps of gonadotropin mediated testosterone biosynthesis were examined in vivo in rats, in relation to Cd dose and time after injection. In the dose–response experiment Male Sprague–Dawley rats received a single subcutaneous (sc) injection of CdCl2 (1, 5 or 10 μmol/kg body weight) and were sacrificed 48 h after injection. A statistically significant decrease in luteinizing hormone (LH) receptor mRNA level in the testicular tissue was demonstrated at the highest dose (10 μmol/kg). In the temporal–response experiment rats were given 10 μmol/kg of CdCl2 sc and sacrificed 0.48, 4.8, 48 or 144 h after injection. LH receptor mRNA levels as well as cyclic adenosine monophosphate (cAMP) levels were found to be significantly lowered at 48 and 144 h. These observations of the mechanisms whereby Cd exerts its effect on the initial steps of testosterone biosynthesis are the first from in vivo experiments.

Keyword
Cadmium; Luteinizing hormone receptor; Cyclic adenosine monophosphate system; Steroidogenesis; Rat; Testis
Identifiers
urn:nbn:se:umu:diva-3524 (URN)10.1016/S0300-483X(02)00440-7 (DOI)
Available from: 2008-10-09 Created: 2008-10-09 Last updated: 2017-12-14Bibliographically approved
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