Chronic morphine administration augments benzodiazepine binding and GABAA receptor function.
Behavioral and neurochemical evidence indicates links between the opioid and GABA neurotransmitter systems. To assess effects of chronic opiates on the major site of postsynaptic GABAergic activity, the GABAA receptor, we administered chronic morphine and naltrexone to mice and evaluated binding at the benzodiazepine and t-butylbicyclophosphorothionate (TBPS) sites and GABA-dependent chloride uptake. After morphine (3 days), benzodiazepine receptor binding in vivo but not in vitro was increased in cortex compared to placebo-treated mice. TBPS binding was unchanged in cortex, but muscimol-stimulated chloride uptake was increased at low doses of muscimol. Benzodiazepine and TBPS binding and muscimol-stimulated chloride uptake were unchanged in naltrexone-(8 days) compared to placebo-treated mice. When naltrexone was administered previously to block opiate sites, the increases in benzodiazepine binding and chloride uptake observed with chronic morphine were reversed. These results indicate that chronic morphine but not naltrexone enhances benzodiazepine binding and GABAA receptor function, perhaps by an action at opioid receptors.
Lopez
F
F
Department of Psychiatry, Tufts University School of Medicine, Boston, MA.
Miller
L G
LG
Thompson
M L
ML
Schatzki
A
A
Chesley
S
S
Greenblatt
D J
DJ
Shader
R I
RI
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides / Q000378:metabolism; D002713:Chlorine; D005445:Flunitrazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D011868:Radioisotopes; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013462:Sulfur Radioisotopes
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D007473:Ion Channels; D011868:Radioisotopes; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; D009118:Muscimol; D002713:Chlorine; D009271:Naltrexone; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate; D009020:Morphine