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.