Influence of chronic opioid treatment on low Km GTPase activity in rat brain: evidence for the involvement of G-proteins in opioid tolerance.
To investigate G protein function during the initial state of opioid tolerance, low Km GTPase activity was measured following chronic treatment with morphine (mu agonist) and butorphanol (mu/delta/kappa mixed agonist) in rats. Chronic opioid administration (20 mg/kg, IP) was performed once a day for 7 consecutive days. Under these conditions, antinociceptive tolerance to morphine but not butorphanol was developed. Chronic morphine treatment enhanced basal low Km GTPase activity in the pons/medulla, but not in the cortex and midbrain. On the other hand, chronic butorphanol treatment had no effect on basal low Km GTPase activity. These results suggest that chronic in vivo treatment of rats with mu agonists leads to an increase in the hydrolysis of GTP to GDP, by a basal low Km GTPase activity of G-proteins in the pons/medulla and that an enhancement of GTPase activity in this specific area may contribute to the development of antinociceptive tolerance to mu agonists.
Makimura
M
M
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Narita
M
M
Feng
Y
Y
Hoskins
B
B
Ho
I K
IK
D000818:Animals; D001921:Brain / Q000187:drug effects; D002077:Butorphanol / Q000494:pharmacology*; D004361:Drug Tolerance; D020558:GTP Phosphohydrolases / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D009020:Morphine; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D002077:Butorphanol