GABA(A) receptor changes in acute allopregnanolone tolerance

European Journal of Pharmacology
V BirznieceGöran Wahlström

Abstract

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 gamma-aminobutyric acid(A) (GABA(A)) receptor subunit alpha4mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the alpha4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the alpha4mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with alpha2mRNA in different hippocampal subregions. There was also a positive relationship between the alpha1mRNA amounts in the different hippocampal subregions, with significant differences between groups. These changes in GABA(A) receptor subunits mRNA expression and protein (alpha4) might be of importance for the development of acute tolerance to allopregnanolone.

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Citations

Aug 28, 2013·Progress in Neurobiology·T BäckströmG van Wingen
Jun 25, 2015·Regulatory Toxicology and Pharmacology : RTP·David V GauvinTheodore J Baird
Jul 13, 2014·European Journal of Pharmacology·Amir H Rezvani, Edward D Levin
Oct 24, 2007·Brain Research·Rajesh R UgaleChandrabhan T Chopde
Oct 5, 2010·British Journal of Pharmacology·Sahruh TurkmenInga-Maj Johansson
Jul 5, 2012·The European Journal of Neuroscience·Bryan W CampHeather A Bimonte-Nelson
Jul 31, 2020·Frontiers in Neuroendocrinology·Inger Sundström-PoromaaEileen Luders

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