GABAA receptor changes in acute allopregnanolone tolerance

To study acute tolerance, rats were anesthetized with interrupted i.v. allopregnanolone infusions where the “silent second” in the electroencephalogram (EEG) was the target. Animals were killed either directly at the first silent second or at the silent second level after 30 or 90 min of anaesthesia. Acute tolerance was demonstrated at 90 min of anaesthesia as earlier shown. In situ hybridization showed a decreased expression of the γ-aminobutyric acidA (GABAA) receptor subunit α4 mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the α4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the α4 mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with α2 mRNA in different hippocampal subregions. There was also a positive relationship between the α1 mRNA amounts in the different hippocampal subregions, with significant differences between groups. These changes in GABAA receptor subunits mRNA expression and protein (α4) might be of importance for the development of acute tolerance to allopregnanolone.