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Allopregnanolone impairs episodic memory in healthy women
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
Department of Psychology, Stockholm University, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi/Olovsson)
2008 (English)In: Psychopharmacology, ISSN 0033-3158, Vol. 199, no 2, 161-168 p.Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is an endogenous neuroactive steroid that, through its binding to the γ-aminobutyric acid (GABA) A receptor, has GABA-active properties. Animal studies indicate that allopregnanolone administration results in diminished learning and memory impairment. The aim of the current study was to investigate the effect of intravenously administered allopregnanolone on episodic memory, semantic memory, and working memory in healthy women.

Twenty-eight healthy women were included in the study. The participants were scheduled for the memory tests twice in the follicular phase. During the test sessions, an intravenous allopregnanolone and placebo infusion were administered in a double-blinded, randomized order at intervals of 48 h. Before and 10 min after the allopregnanolone/placebo injections, memory tasks were performed.The study demonstrated that allopregnanolone impaired episodic memory in healthy women. There was a significant difference between pre- and postallopregnanolone injection episodic memory scores (p < 0.05), whereas there was no change in episodic memory performance following the placebo injections. There was also a significant difference between allopregnanolone and placebo postinjection episodic memory scores (p < 0.05). There were no effects of allopregnanolone on the semantic memory task or working memory task.Intravenous allopregnanolone impairs episodic memory in healthy women, but there is a high degree of individual variability.

Place, publisher, year, edition, pages
2008. Vol. 199, no 2, 161-168 p.
Keyword [en]
Allopregnanolone, Healthy women, Follicular phase of menstrual cycle, Episodic memory, Semantic memory, Working memory, Estradiol, Progesterone
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-97756DOI: 10.1007/s00213-008-1150-7ISI: 000257383100003OAI: oai:DiVA.org:uu-97756DiVA: diva2:172814
Available from: 2008-11-14 Created: 2008-11-14 Last updated: 2009-10-29Bibliographically approved
In thesis
1. Hormones, Mood and Cognition
Open this publication in new window or tab >>Hormones, Mood and Cognition
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition.

In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated.

Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects.

The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal.

Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning.

The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI.

We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase.

Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women.

In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 91 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 394
startle response; prepulse inhibition; premenstrual dysphoric disorder; menstrual cycle; pregnancy; postpartum period; episodic memory; semantic memory; working memory; progesterone; estradiol; allopregnanolone.
National Category
Clinical Science
urn:nbn:se:uu:diva-9365 (URN)978-91-554-7332-7 (ISBN)
Public defence
2008-12-05, Rosénsalen, Uppsala University Hospital, Entrance 95/96, Uppsala, 13:15
Available from: 2008-11-14 Created: 2008-11-14Bibliographically approved

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