GABA(A) 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 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.
Birzniece
Vita
V
Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University Hospital, SE 901 85, Sweden.
Türkmen
Sahruh
S
Lindblad
Charlotte
C
Zhu
Di
D
Johansson
Inga-Maj
IM
Bäckström
Torbjörn
T
Wahlström
Göran
G
D000777:Anesthetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D018891:Dentate Gyrus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007262:Infusions, Intravenous; D008297:Male; D011280:Pregnanolone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D021122:Protein Subunits / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000032:analysis / Q000235:genetics*; D018080:Receptors, GABA-B / Q000032:analysis / Q000235:genetics; D020651:Ventral Thalamic Nuclei / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D000777:Anesthetics; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D011280:Pregnanolone