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 tot...

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Bibliographic Details
Published inLife sciences (1973) Vol. 31; no. 20-21; p. 2287
Main Authors Ritzmann, R F, Lee, J M, Fields, J Z
Format Journal Article
LanguageEnglish
Published Netherlands 01.11.1982
Subjects
Analgesia
Animals
Corpus Striatum - drug effects
Corpus Striatum - physiology
Dipeptides - pharmacology
Dopamine - physiology
Humans
Hypothalamus - drug effects
Hypothalamus - physiology
Male
Morphine - pharmacology
Neuropeptides
Peptides, Cyclic
Rats
Rats, Inbred Strains
Receptors, Dopamine - drug effects
Receptors, Dopamine - metabolism
Spiperone - metabolism
Stereotyped Behavior - drug effects
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Summary: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.
ISSN:0024-3205
DOI:10.1016/0024-3205(82)90139-4