Morphine and methadone dependence in the rat: withdrawal and brain met-enkephalin levels.
Opioids were administered to female Long Evans rats in their drinking water. Maintenance doses of 0.8 and 0.4 mg/ml for morphine and methadone, respectively, were achieved using an ascending dosage schedule. Rats were decapitated 0, 20, or 60 min after naloxone (10 mg/kg, IP) or saline. Brain met-enkephalin-like immunoreactivity (ME-LI) was determined by radioimmunoassay (RIA). In morphine-drinking animals, ME-LI in all regions of the brain was unaltered following saline administration; however, 20 min after naloxone injection ME-LI had increased in the striatum, hypothalamus, midbrain, and pituitary. By 60 min, ME-LI was no longer elevated. In both methadone- and water-drinking rats, ME-LI did not deviate from normal. These elevated levels of ME-LI, 20 min after naloxone-precipitated withdrawal in morphine-dependent rats, coincided with the peak of behavioural signs in the precipitated withdrawal syndrome. The milder behavioural disturbances observed in the withdrawal of methadone-drinking rats were consistent with the unaltered ME-LI in these animals.
Pierce
T L
TL
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Tiong
G K
GK
Olley
J E
JE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D004744:Enkephalin, Methionine / Q000378:metabolism*; D005260:Female; D008691:Methadone / Q000008:administration & dosage; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology
D009270:Naloxone; D004744:Enkephalin, Methionine; D009020:Morphine; D008691:Methadone