Cyclo(Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine: agonist binding to D2 dopamine receptors correlates with stereotypic behavior.
We have previously shown that MIF and its structural analog, cyclo-(Leu-Gly), block analgesic tolerance and some signs of physical dependence following chronic opiate administration. The mechanism of action of these peptides has not been clearly elucidated. The data presented here suggests that chronic opiate administration causes a behavioral supersensitivity to dopamine (DA) agonists which is highly correlated with an increase in D2-Hi receptor affinity for DA agonists, but not antagonists. Both the behavioral and receptor changes are blocked by prior administration of cyclo(Leu-Gly). This suggests that the ability of cyclo(Leu-Gly) to block the development of opiate addictive states may involve DA synaptic elements.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology*; D004361:Drug Tolerance; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2
D004151:Dipeptides; D009479:Neuropeptides; D010456:Peptides, Cyclic; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D009270:Naloxone; C021166:cyclo(leucylglycine); D009020:Morphine