In many women, aversive psychological and somatic symptoms develop during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. Following intravenous administration in anaesthetised rats, the progesterone metabolite allopregnanolone readily gained access to the periaqueductal grey (PAG), a region involved in generating panic-like anxiety, and inhibited neural activity via actions at GABA(A) receptors. Withdrawal of female rats from prolonged systemic dosing with progesterone leads to increased numbers of alpha4, beta1 and delta GABA(A) receptor subunit-immunoreactive neurones in the PAG. In naturally cycling rats a similar upregulation occurred during late dioestrus, when progesterone levels fall. Functional experiments revealed that upregulation of alpha4beta1delta receptor subunit expression was associated with a decrease in GABAergic tone in the PAG and increased responsiveness to a panicogenic CCK(2) receptor agonist. The oestrous cycle-linked plasticity of GABA receptors was absent in rats housed in quiet conditions in an isolated room suggesting that environmental factors may be able to influence the central response to hormonal changes. In susceptible animals, i.e. those housed in a communal animal holding room, oestrous cycle-related changes in GABAergic circuits may underlie the development of increased anxiety levels that represent a rodent counterpart to premenstrual syndrome in women.