Footshock- and psychological-stress prevent the development of tolerance to spinal but not supraspinal morphine.
The site of action involved in the suppression by exposure to footshock (FS)- and psychological (PSY)-stress of the development of antinociceptive tolerance to morphine has been investigated. Daily treatment with 10 mg/kg, s.c.; 3 micrograms, i.t.; and 5 micrograms, i.c.v. of morphine, regardless of the administration route, resulted in the development of tolerance. Daily exposure to FS- or PSY-stress suppressed the development of tolerance to s.c. and i.t. administered morphine but not that to i.c.v. administered morphine. Pretreatment with 2 mg/kg, i.p. of nor-binaltorphimine (nor-BNI) abolished the suppressive effect of PSY-stress on the development of tolerance to morphine given s.c. The suppression by PSY-stress was also antagonized by 2 micrograms, i.t. of nor-BNI and not by 2 micrograms, i.c.v. of nor-BNI. Thus, the development of tolerance in the spinal cord due to interaction of morphine at mu-opioid receptors can be suppressed by exposure to these stresses, probably through the descending signals from the supraspinal area, and activation of kappa-opioid receptors in the spinal cord could also participate in the suppression by PSY-stress.
Takahashi
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Kaneto
H
H
D000818:Animals; D004333:Drug Administration Routes; D004361:Drug Tolerance; D004597:Electroshock; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology*
D011957:Receptors, Opioid; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine