Steady-state methadone in rats does not change mRNA levels of corticotropin-releasing factor, its pituitary receptor or proopiomelanocortin.
Male Fischer rats received either methadone (a long-acting opioid agonist, 10 mg/kg/day) or saline (24 microliters/day) subcutaneously by osmotic minipumps for 7 days. Chronic steady-state methadone administration did not alter (a) corticotropin-releasing factor (CRF) mRNA in the hypothalamus, (b) proopiomelanocortin (POMC) and CRF type 1 receptor (CRF-R1) mRNAs in the anterior lobe and neurointermediate/posterior lobe of the pituitary, or (c) circulating levels of corticosterone. No change was found in levels of either POMC mRNA in the hypothalamus and amygdala, or CRF mRNA in the frontal cortex, olfactory bulb and amygdala. These results demonstrate that neither the activity of the hypothalamic-pituitary-adrenal axis, nor the beta-endorphin and CRF systems in the brain, are altered by steady-state occupancy of opioid receptors with the long-acting opioid agonist methadone.
Zhou
Y
Y
Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA.
Spangler
R
R
Maggos
C E
CE
LaForge
K S
KS
Ho
A
A
Kreek
M J
MJ
D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*
D009294:Narcotics; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D008691:Methadone; D003345:Corticosterone