Oxytocin and a C-terminal derivative (Z-prolyl-d-leucine) attenuate tolerance to and dependence on morphine and interact with dopaminergic neurotransmission in the mouse brain

G. L. Kovács, Zsuzsanna Horváth, Z. Sarnyai, Mária Faludi, Gyula Telegdy

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Abstract

The effects of oxytocin (OXT) and of dipeptides derived from the C-terminal portion of oxytocin (Z-prolyl-leucine and Z-prolyl-d-leucine) on the development of acute and chronic tolerance to, and dependence on morphine were tested in the mouse. Oxytocin and the dipeptides attenuated the development of acute and chronic tolerance to the antinociceptive effect of morphine and delayed the onset of the naloxone-precipitated withdrawal syndrome. Both oxytocin and Z-prolyl-d-leucine affected drug-induced behavioural responses related to dopamine (DA) in the brain. Thus, oxytocin potentiated the hypermotility induced by a large dose of apomorphine and decreased the supersensitivity of the DA receptors. Small doses of Z-prolyl-d-leucine inhibited the hypomotility elicited by a small dose of apomorphine and potentiated the hyperactivity induced by amphetamine. The data indicate that both oxytocin and Z-prolyl-d-leucine affect tolerance to and dependence on morphine. While oxytocin interacts mainly with postsynaptic DA-ergic neuronal elements, the dipeptide primarily affects DA-ergic neurotransmission at the presynaptic level.

Original languageEnglish
Pages (from-to)413-419
Number of pages7
JournalNeuropharmacology
Volume24
Issue number5
DOIs
Publication statusPublished - May 1985

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Keywords

  • Z-prolyl-d-leucine
  • amphetamine
  • apomorphine
  • dependence
  • morphine
  • oxytocin
  • tolerance

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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