Effects of L-DOPA and bromocriptine on haloperidol-induced motor deficits in mice

Tsuneyasu Kobayashi, Tsutomu Araki, Yasuto Itoyama, Mitsuhiro Takeshita, Tomihisa Ohta, Yoshiteru Oshima

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Abstract

L-3,4-Dihydroxyphenylalanine (L-DOPA), the precursor of dopamine, and bromocriptine, a dopamine D2 receptor agonist, were investigated in haloperidol-induced motor impairments in mice using both catalepsy and pole tests. In catalepsy test, subcutaneous treatment with haloperidol (0.125, 0.25 and 0.5 mg/kg) caused a cataleptic effect in mice in a dose-dependent manner. This cataleptic effect was evident upto 7 hr after haloperidol treatment. In pole test, haloperidol (0.125, 0.25 and 0.5 mg/kg) produced the prolongation of Tturn and TLA as a marker of bradykinesia in mice and the prolongation lasted at least 7 hr after haloperidol treatment. Intraperitoneal co-pretreatment with L-DOPA (400 mg/kg) + carbidopa (10 mg/kg) in mice decreased the catalepsy induced by haloperidol at a dose of 0.125 mg/kg, while co-pretreatment with L-DOPA (200 and 400 mg/kg) + carbidopa (10 mg/kg) dose-dependently decreased the haloperidol (0.125 mg/kg)-induced bradykinesia. The effect of L-DOPA + carbidopa in pole test was more pronounced than that in catalepsy test. Intraperitoneal pretreatment with bromocriptine (2 and 4 mg/kg) in mice reduced the catalepsy and bradykinesia produced by haloperidol at a dose of 0.125 mg/kg. The effect of bromocriptine in pole test was relatively similar to that in catalepsy test. Also, co-pretreatment with L-DOPA (400 mg/kg) + carbidopa (10 mg/kg) and pretreatment with bromocriptine (2 and 4 mg/kg) significantly decreased the catalepsy induced by haloperidol at a higher dose of 0.5 mg/kg. These results indicate that co-administration with L-DOPA + carbidopa and single treatment with bromocriptine can decrease haloperidol-induced catalepsy and bradykinesia in mice. Furthermore, our study suggests that pole test as well as catalepsy test is of value in the screening of drugs against neuroleptic- induced motor deficits.

Original languageEnglish
Pages (from-to)2529-2538
Number of pages10
JournalLife Sciences
Volume61
Issue number26
DOIs
Publication statusPublished - 1997 Nov 21

Keywords

  • Bromocriptine
  • Carbidopa
  • Catalepsy
  • Haloperidol
  • L-dopa
  • Motor deficiency
  • Pole test

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Kobayashi, T., Araki, T., Itoyama, Y., Takeshita, M., Ohta, T., & Oshima, Y. (1997). Effects of L-DOPA and bromocriptine on haloperidol-induced motor deficits in mice. Life Sciences, 61(26), 2529-2538. https://doi.org/10.1016/S0024-3205(97)01007-2