Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats

Psychopharmacology (Berl). 1989;99(3):357-61. doi: 10.1007/BF00445557.


The biological activity of beta-casein derived beta-casomorphin peptides was evaluated by injecting bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), the homologous sequence in human beta-casein (Tyr-Pro-Phe-Val-Glu) and the corresponding N-terminal tetrapeptides into the left substantia nigra of rats. Their ability to produce rotational behaviour was compared to that produced by three reference compounds, morphine, D-ala2D-leu5 enkephalin and U50,488H, ligands for mu, delta and kappa types of opioid receptors, respectively. The relative potencies of beta-casomorphins and morphine were compared to those tested in two in vitro assays for opioid activity: (1) inhibition of the electrically induced contraction of the isolated myenteric plexus-longitudinal muscle of the guinea-pig ileum and (2) displacement of 3H-dihydromorphine binding to brain membranes. The same ranking order of potency was found in all three assays, the peptides from human beta-casein being about 10-fold less potent than those from bovine beta-casein. The effects of both morphine and bovine beta-casomorphin-5 in producing rotational behaviour were antagonized by naloxone; however, approximately 10-fold more naloxone was required to antagonize the beta-casomorphin-5 effect than that of morphine. The present data are discussed in the light of the recent observation that high concentrations of beta-casomorphin-like peptides are found in the cerebrospinal fluid and plasma of women with postpartum psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Animals
  • Cattle
  • Endorphins / administration & dosage
  • Endorphins / pharmacology*
  • Enkephalin, Leucine / analogs & derivatives
  • Enkephalin, Leucine / pharmacology
  • Enkephalin, Leucine-2-Alanine* / analogs & derivatives*
  • Guinea Pigs
  • Humans
  • Ileum / drug effects
  • In Vitro Techniques
  • Injections
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Morphine / pharmacology
  • Muscle, Smooth / drug effects
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism
  • Rotation
  • Stereotyped Behavior / drug effects*
  • Substantia Nigra


  • Endorphins
  • Pyrrolidines
  • Receptors, Opioid
  • Enkephalin, Leucine
  • Enkephalin, Leucine-2-Alanine
  • enkephalinamide-Leu, Ala(2)-
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • beta-casomorphins