In women, susceptibility to panicogenic challenge increases when progesterone levels fall sharply during the late luteal phase of the menstrual cycle (Follesa et al. 2001; Le Melledo et al. 2000). In rats, the dorsal half of the periaqueductal grey matter (PAG) contains neural circuitry that can initiate panic-like behaviour (Lovick 2000). In female rats, we found that the fall in progesterone levels during late dioestrus is associated with increased numbers of α4 and δ GABA_A-receptor subunit immunoreactive neurones in the PAG (Griffiths et al. 2002). In other regions of the brain α4 subunits are associated with receptors containing β1 subunits (Bencsits et al. 1999). We have therefore investigated whether plasticity of β1 receptor subunit expression occurs in the PAG during the oestrous cycle.

Urethane-anaesthetised female rats (1 g kg^-1 I.P.) were humanely killed by perfusion with 100 ml heparinised (100 U ml^-1) saline followed by 4 % paraformaldehyde in 0.1 M phosphate buffer. The stage of the oestrous cycle was determined from vaginal cytology. Frozen sections of midbrain 40 µm thick were processed to reveal immunoreactivity for β1 subunits using antibody sc-7361 N-19 (Santa Cruz Biotechnology). Immunostaining was revealed using a biotinylated secondary antibody and diaminobenzidene as the chromogen.

During the early stages of the oestrous cycle the number of β1 immunoreactive cells in the PAG remained relatively constant, ranging from 32.3 ± 2.0 cells (0.05 mm²)^-1, mean ± S.E.M., in proestrus to 28.4 ± 1.2 cells (0.05 mm²)^-1 in early dioestrus (5 rats per stage). However there was a 67 % increase to 47.4 ± 1.8 cells (0.05 mm²)^-1 in late dioestrus compared to early dioestrus (n = 5, P < 0.0001 ANOVA with Bonferroni-Dunn).

These findings are in line with our previous data on plasticity of α4 and δ receptor subunit expression in the PAG (Griffiths et al. 2002). Moreover, they raise the possibility that falling progesterone levels during late dioestrus lead to increased expression of an aberrant receptor within the PAG in which α4, β1 and δ subunits co-assemble. Recombinant α4β1δ GABA_A receptors show an atypical pharmacology (Dunn, Tancowny & Martin, this meeting). In the PAG, a disturbance of GABAergic control associated with the expression of this receptor subtype may contribute to an increased susceptibility to panicogenic challenge.

This work was supported by the British Heart Foundation