Autoradiographic analysis of GABAA receptors in mu-opioid receptor knockout mice.
Anatomical evidence indicates that gamma-aminobutyric acid (GABA)-ergic and opioidergic systems are closely linked and act on the same neurons. However, the regulatory mechanisms between GABAergic and opioidergic system have not been well characterized. In the present study, we investigated whether there are changes in GABA(A) receptors in mice lacking mu-opioid receptor gene. The GABA(A) receptor binding was carried out by autoradiography using [(3)H]-muscimol (GABA(A)), [(3)H]-flunitrazepam (FNZ, native type 1 benzodiazepine) and [(35)S]-t-butylbicyclophosphorothionate (TBPS, binding to GABA(A)-gated chloride channels) in brain slices of wild type and mu-opioid receptor knockout mice. The binding of [(3)H]-FNZ in mu-opioid receptor knockout mice was significantly higher than that of the wild type controls in most of the cortex and hippocampal CA1 and CA2 formations. mu-Opioid receptor knockout mice show significantly lower binding of [(35)S]-TBPS than that of the wild type mice in few of the cortical areas including ectorhinal cortex layers I, III, and V, but not in the hippocampus. There was no significant difference in binding of [(3)H]-muscimol between mu-opioid receptor knockout and wild type mice in the cortex and hippocampus. These data indicate that there are specific regional changes in GABA(A) receptor binding sites in mu-opioid receptor knockout mice. These data also suggest that there are compensatory up-regulation of benzodiazepine binding site of GABA(A) receptors in the cortex and hippocampus and down-regulation of GABA-gated chloride channel binding site of GABA(A) receptors in the cortex of the mu-opioid receptor knockout mice.
Tien
Lu-Tai
LT
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA. lutaitien@yahoo.com
Ma
Tangeng
T
Fan
Lir-Wan
LW
Loh
Horace H
HH
Ho
Ing-Kang
IK
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology; D015536:Down-Regulation; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009118:Muscimol / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000502:physiology*; D014316:Tritium; D015854:Up-Regulation
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D014316:Tritium; D009118:Muscimol; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate