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

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

Research output: Contribution to journalArticle

239 Citations (Scopus)

Abstract

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
Volume49
Issue number4
DOIs
Publication statusPublished - Jun 15 1978

Fingerprint

Endorphins
Neuropeptides
Antipsychotic Agents
Avoidance Learning
Hand Strength
Haloperidol
Walking
Opiate Alkaloids
Methionine Enkephalin
Neuropeptide Y

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Neuroleptic activity of the neuropeptide β-LPH62-77 ([Des-Tyr1]γ-endorphin; DTγE). / De Wied, David; Kovács, G.; Bohus, Bela; Van Ree, Jan M.; Greven, Henk M.

In: European Journal of Pharmacology, Vol. 49, No. 4, 15.06.1978, p. 427-436.

Research output: Contribution to journalArticle

De Wied, David ; Kovács, G. ; Bohus, Bela ; Van Ree, Jan M. ; Greven, Henk M. / Neuroleptic activity of the neuropeptide β-LPH62-77 ([Des-Tyr1]γ-endorphin; DTγE). In: European Journal of Pharmacology. 1978 ; Vol. 49, No. 4. pp. 427-436.
@article{8f04138cc8094d3daef3b3e06a6d7876,
title = "Neuroleptic activity of the neuropeptide β-LPH62-77 ([Des-Tyr1]γ-endorphin; DTγE)",
abstract = "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.",
keywords = "Avoidance behavior, Endogenous neuroleptic, Endorphins, Haloperidol, Neuroleptic activity",
author = "{De Wied}, David and G. Kov{\'a}cs and Bela Bohus and {Van Ree}, {Jan M.} and Greven, {Henk M.}",
year = "1978",
month = "6",
day = "15",
doi = "10.1016/0014-2999(78)90317-5",
language = "English",
volume = "49",
pages = "427--436",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Neuroleptic activity of the neuropeptide β-LPH62-77 ([Des-Tyr1]γ-endorphin; DTγE)

AU - De Wied, David

AU - Kovács, G.

AU - Bohus, Bela

AU - Van Ree, Jan M.

AU - Greven, Henk M.

PY - 1978/6/15

Y1 - 1978/6/15

N2 - 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.

AB - 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.

KW - Avoidance behavior

KW - Endogenous neuroleptic

KW - Endorphins

KW - Haloperidol

KW - Neuroleptic activity

UR - http://www.scopus.com/inward/record.url?scp=0018256128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018256128&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(78)90317-5

DO - 10.1016/0014-2999(78)90317-5

M3 - Article

C2 - 27374

AN - SCOPUS:0018256128

VL - 49

SP - 427

EP - 436

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 4

ER -