Neuroleptic activity of the neuropeptide β-LPH62-77 ([Des-Tyr1]γ-endorphin; DTγE)

David De Wied, Gabor L. Kovács, Bela Bohus, Jan M. Van Ree, Henk M. Greven

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In contrast to β-endorphin, α-endorphin, β-LPH61-69 and Met-enkephalin which delay extinction of pole-jumping avoidance behavior (De Wied et al., 1978), γ-endorphin given either subcutaneously (30 ng/rat) or intraventricularly (0.3 ng/rat) facilitated extinction. Removal of the N-terminal amino acid residue tyrosine - yielding the neuropeptide [Des-Tyr1]γ-endorphin (DTγE) - which destroys the opiate-like activity as determined on the electrically driven guinea pig ileum, potentiated the facilitating effect of γ-endorphin on pole-jumping avoidance behavior. Observations on passive avoidance behavior gave essentially the same results. Whereas α-endorphin facilitated this behavior. DTγE attenuated passive avoidance behavior. Amounts of γ-endorphin and DTγE which were highly active on extinction of pole-jumping avoidance behavior (0.3 μg s.c. per rat) were without effect on gross behavior in an open field. Much higher amounts (10-50 μg s.c. per rat) also failed to affect the rate of ambulation in an open field. In relatively high doses (20 μg i.v.t. or 50 μg s.c. per rat), γ-endorphin and in particular DTγE were positive in the various "grip tests". Haloperidol given s.c. (0.03-0.1 μg/rat) facilitated extinction of pole-jumping avoidance behavior and attenuated passive avoidance behavior. The same amounts decreased ambulation in an open field. In higher doses haloperidol was active in the "grip tests" but in addition caused severe immobility, ptosis and extension of the lower limbs. Intraventricularly administered morphine or β-endorphin induced wide open eyes, exophthalmus, rigidity and reduced reflexes, in contrast to γ-endorphin and DTγE which did not produce such effects. These results are interpreted to indicate that DTγE or a closely related peptide is an endogenous neuroleptic. It may be that a reduced availability as a result of an inborn error in the generation of DTγE is an etiological factor in psychopathological states for which neuroleptic drugs are beneficial.

Original languageEnglish
Pages (from-to)427-436
Number of pages10
JournalEuropean Journal of Pharmacology
Issue number4
Publication statusPublished - Jun 15 1978


  • Avoidance behavior
  • Endogenous neuroleptic
  • Endorphins
  • Haloperidol
  • Neuroleptic activity

ASJC Scopus subject areas

  • Pharmacology

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