Chronic, but not acute, administration of morphine alters antiopiate (Tyr-MIF-1) binding sites in rat brain.
Opiate addiction could involve a change in the binding of endogenous antiopiates. A candidate for such a role is Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), a brain peptide that can antagonize exogenous and endogenous opiates and bind to opiate receptors. Its primary action, however, may be through its own binding site in brain, which we now report is altered by chronic administration of morphine. Rats given morphine pellets had reduced binding of both iodinated and tritiated Tyr-MIF-1 on day 5, when substantial tolerance is evident. In contrast, mu and delta opiate receptors were increased. Acute injection of an analgesic dose of morphine did not reduce Tyr-MIF-1 binding, indicating that chronic administration is required for the change. These findings open new approaches to the study of addiction by focusing on antiopiate activity.
Zadina
J E
JE
Veterans Administration Medical Center, New Orleans, LA.
Kastin
A J
AJ
Ge
L J
LJ
Gulden
H
H
Bungart
K J
KJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone