On the mode of action of an oxytocin derivative (Z-Pro-D-Leu) on morphine-dependence in mice

G. Kovács, Lucia Szontágh, L. Baláspiri, K. Pintye-Hódi, P. Bohus, G. Telegdy

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The dipeptide Z-Pro-D-Leu appears to attenuate the development of physical dependence on morphine in mice, as measured by the stereotyped jumping response after naloxone challenge. Injected subcutaneously, 50 μg Z-Pro-D-Leu was required to produce this effect, while a hundred times smaller amount injected into the cerebral ventricles was sufficient to produce the same effect. In morphine-naive mice, 50 μg of the dipeptide did not change the dose-response curve for morphine, measured by the antinociceptive effect of the opiate on a hot-plate test. Although Z-Pro-D-Leu per se did not induce antinociception in the doses tested (50, 100 and 200 μg), the larger doses potentiated the effect of morphine. As a possible mode of the central action, the effect of the dipeptide on the levels of noradrenaline (NA) dopamine (DA) and serotonin (5-HT) in the brain has been measured. Two hours after a single acute injection of Z-Pro-D-Leu (50 μg), the level of NA in the lower brain stem (pons + medulla) was significantly reduced. Daily administration of the dipeptide for 3 days resulted in decreases in the levels of NA and DA in the brain stem. In morphine-dependent mice, the 5-HT and DA levels in the brain stem were reduced 30 min after naloxone challenge. The data support the idea that Z-Pro-D-Leu inhibits the development of morphine-dependence by a mechanism of action in the central nervous system. This effect seems to be distinct from an antagonism between the dipeptide and morphine at the receptor level. It is likey, on the other hand, that the effect is related to an influence of the dipeptide on monoaminergic neurotransmission in the brain stem.

Original languageEnglish
Pages (from-to)647-651
Number of pages5
JournalNeuropharmacology
Volume20
Issue number7
DOIs
Publication statusPublished - 1981

Fingerprint

prolylleucine
Morphine Dependence
Dipeptides
Oxytocin
Morphine
Brain Stem
Dopamine
Serotonin
Norepinephrine
Naloxone
Opiate Alkaloids
Cerebral Ventricles
Pons
mu Opioid Receptor
Synaptic Transmission
Central Nervous System
Injections
Brain

Keywords

  • 5-HT
  • brain stem NA
  • DA
  • morphine withdrawal
  • Z-Pro-D-Leu

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

On the mode of action of an oxytocin derivative (Z-Pro-D-Leu) on morphine-dependence in mice. / Kovács, G.; Szontágh, Lucia; Baláspiri, L.; Pintye-Hódi, K.; Bohus, P.; Telegdy, G.

In: Neuropharmacology, Vol. 20, No. 7, 1981, p. 647-651.

Research output: Contribution to journalArticle

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