Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile

N. Ogawa, K. Haba, Masato Asanuma, A. Mori

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 μg/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals. The observed beneficial effect of ceruletide on impaired neuronal pathways indicates that it acts as a 'neuro-normalizer' in the animal model of IDPN-induced dyskinesia.

Original languageEnglish
Pages (from-to)271-279
Number of pages9
JournalBrain Research
Volume556
Issue number2
DOIs
Publication statusPublished - Aug 16 1991

Fingerprint

Ceruletide
Dyskinesias
Head
3,4-Dihydroxyphenylacetic Acid
Hydroxyindoleacetic Acid
Hippocampus
Cholecystokinin
Neurotransmitter Agents
Half-Life
Animal Models
Brain

Keywords

  • Ceruletide
  • Dopaminergic neuronal function
  • Dyskinesia
  • Iminodipropionitrile
  • Long-lasting effect
  • Serotonergic neuronal function

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

Cite this

Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile. / Ogawa, N.; Haba, K.; Asanuma, Masato; Mori, A.

In: Brain Research, Vol. 556, No. 2, 16.08.1991, p. 271-279.

Research output: Contribution to journalArticle

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