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Cyclical changes in production of neuroactive steroids during the oestrous cycle induce significant changes in  GABA A  receptor expression in female rats. In the periaqueductal grey (PAG) matter, upregulation of  α 4 β 1 δ  GABA A  receptors occurs as progesterone levels fall during late dioestrus (LD) or during withdrawal from an exogenous progesterone dosing regime. The new receptors are likely to be extrasynaptically located on the GABAergic interneurone population and to mediate tonic currents. Electrophysiological studies showed that when  α 4 β 1 δ  GABA A  receptor expression was increased, the excitability of the output neurones in the PAG increased, due to a decrease in the level of ongoing inhibitory tone from the GABAergic interneurones. The functional consequences in terms of nociceptive processing were investigated in conscious rats. Baseline tail flick latencies were similar in all rats. However, acute exposure to mild vibration stress evoked hyperalgesia in rats in LD and after progesterone withdrawal, in line with the upregulation of  α 4 β 1 δ  GABA A  receptor expression.

Progesterone Withdrawal-Evoked Plasticity of Neural Function in the Female Periaqueductal Grey Matter