Evaluation of the antibradykinetic actions of 5-HT1A agonists using the mouse pole test.

Abstract

To clarify the role and mechanism of the 5-HT1A receptor in modulating extrapyramidal motor disorders, we studied the actions of 5-HT1A agonists in the mouse pole test, a valid model of parkinsonian bradykinesia. Haloperidol markedly delayed pole-descending behavior of mice in the pole test, and this effect was alleviated by the antiparkinsonian agent trihexyphenidyl (a muscarinic antagonist). The selective 5-HT1A agonists, 8-hydroxydipropylaminotetraline (8-OH-DPAT) and tandospirone, significantly attenuated haloperidol-induced bradykinesia in a dose-dependent manner. The alleviation of haloperidol-induced bradykinesia by 8-OH-DPAT was completely antagonized by WAY-100135 (a selective 5-HT1A antagonist), but was unaffected by cerebral 5-HT depletion with p-chlorophenylalanine (PCPA) treatment (300 mg/kg, i.p. for 3 days). These results suggest that 5-HT1A agonists improve extrapyramidal motor disorders associated with antipsychotic treatments by stimulating the postsynaptic 5-HT1A receptor.

• Authors: Yukihiro Ohno, Saki Shimizu, Junta Imaki, Shizuka Ishihara, Nobumasa Sofue, Masashi Sasa, Yoshiko Kawai
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 32 Issue 5 Pg. 1302-7 (Jul 01 2008) ISSN: 0278-5846 [Print] England
• PMID: 18495311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Isoindoles
• Muscarinic Antagonists
• Piperazines
• Pyrimidines
• Serotonin Antagonists
• Serotonin Receptor Agonists
• WAY 100135
• tandospirone
• Serotonin
• Trihexyphenidyl
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Haloperidol
• Fenclonine

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (therapeutic use)
• Animals
• Antipsychotic Agents (toxicity)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fenclonine (pharmacology)
• Haloperidol (toxicity)
• Hypokinesia (chemically induced, drug therapy)
• Isoindoles (therapeutic use)
• Male
• Mice
• Motor Activity (drug effects)
• Muscarinic Antagonists (therapeutic use)
• Piperazines (pharmacology, therapeutic use)
• Pyrimidines (therapeutic use)
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (therapeutic use)
• Trihexyphenidyl (therapeutic use)