1. ¹FC Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands
2. ²Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
3. ³Department of Clinical Science, Obstetrics and Gynecology, Umeå Neurosteroid Research Center, Norrlands University Hospital, Umeå, Sweden
4. ⁴Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Correspondence: GA van Wingen, FC Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Kapittelweg 29, Nijmegen 6525 EN, The Netherlands. E-mail: guido.vanwingen@fcdonders.ru.nl

Received 19 September 2006; Revised 10 April 2007; Accepted 12 April 2007; Published online 19 June 2007.

Abstract

The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of -aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.