Peptide inhibition of morphine-induced dopaminergic supersensitivity

Injection of the peptide cyclo(Leu-Gly) into rats prior to chronic exposure to morphine, inhibits: 1) the development of analgesic tolerance; 2) some signs of physical dependence; and, 3) morphine-induced increases in behavioral responses to dopamine agonists. Although there was no change in the total number of high affinity striatal dopamine receptors, chronic morphine treatment did increase the affinity of the ligand at the receptor. The peptide blocked not only the affinity change, but the increased behavioral response to apomorphine as well. These behavioral changes correlate significantly with the neurochemical changes in dopamine receptors following chronic morphine treatment. Therefore, some of the pharmacological efforts of morphine may be mediated by changes in CNS dopamine receptors and that the peptides may act by inhibiting these neurochemical changes.