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This Article Full Text Full Text (PDF) All Versions of this Article: 91/4/655    most recent expphysiol.2005.032342v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lovick, T. A. Search for Related Content PubMed PubMed Citation Articles by Lovick, T. A. Related Collections Neuroendocrinology/Endocrinology Hot Topic Reviews

¹ Division of Medical Science, Physiology, University of Birmingham, Birmingham B15 2TT, UK

Many women experience psychological changes during the luteal phase of their menstrual cycle. The late luteal (premenstrual) phase, when symptoms become most severe, is characterized by declining levels of ovarian progesterone. In female rats, withdrawal from prolonged dosing with progesterone leads to upregulation of 4 and subunits of the GABA_A receptor in several brain regions. During the oestrous cycle of the rat, the natural fall in progesterone that occurs in late dioestrus is associated with a parallel increase in expression of 4, ß1 and GABA_A receptor subunits in neurones in the periaqueductal grey matter (PAG), suggesting that new receptors of the 4ß1 composition have been formed. Recombinant 4ß1 receptors display a low EC₅₀ for GABA, which is consistent with activation by extracellular levels of GABA. They are also likely to be located extrasynaptically and to carry tonic currents. In the PAG, a region involved in mediating panic-like anxiety, 4, ß1 and GABA_A receptor subunits are located principally on GABAergic interneurones. On-going GABAergic neuronal activity normally limits and controls the excitability of the panic circuitry. During late dioestrus, when expression of 4, ß1 and subunits on GABAergic interneurones is upregulated, the increase in tonic current would be expected to lead to a reduction in the activity of the GABAergic population. Thus the panic circuitry would become intrinsically more excitable. It is suggested that during the menstrual cycle in women, plasticity of GABA_A receptor subunit expression in brain regions such as the PAG, which are involved in mediating anxiety behaviour, may underlie some of the changes in mood that occur during the premenstrual period.

(Received 27 January 2006; accepted after revision 15 May 2006; first published online 1 June 2006)
Corresponding author T. A. Lovick: Division of Medical Science, Physiology, University of Birmingham, Birmingham B15 2TT, UK. Email: t.a.lovick{at}bham.ac.uk