Inhibitory effect of 17β-estradiol in the parabrachial nucleus is mediated by GABA

In the present investigation, electrophysiological recordings of thalamic relay neurons were used to investigate the role of estrogen as a modulator of visceral afferent information through the PBN to forebrain structures. Experiments were done in anaesthetized (sodium thiobutabarbitol; 100 mg/kg) male and ovariectomized female rats supplemented for 7 days prior with either 17β-estradiol (OVX-E 2) or saline (OVX-S). A portion of the right cervical vagus was isolated for the electrical activation (0.8 Hz, 2 ms duration) of visceral afferents. The evoked single and multi-unit activity was recorded via a recording electrode in the ventrobasal thalamus. Exogenous microinjection of 17β-estradiol (0.1, 0.25 and 0.5 μM; 200 nl) into the parabrachial nucleus (PBN) produced a significant, dose-dependent attenuation in the magnitude of visceral afferent activation-evoked responses of neurons recorded in the thalamus in both male and OVX-E 2 groups. No effect on evoked thalamic activity was observed following injection of estrogen into the PBN of OVX-S animals. Co-injection of estrogen with the GABA A receptor antagonist, bicuculine (0.1 μM; 200 nl) but not phaclofen (GABA B; 0.1, 0.5 or 1 μM; 200 nl) resulted in an increase in the evoked thalamic response in males (55±11%) and OVX-E 2 female (68±15%) rats. These studies suggest that estrogen inhibits neurotransmission in the PBN via an interaction with the GABA A receptor to modulate the flow of visceral information to the thalamus.