Evaluation of the antibradykinetic actions of 5-HT1A agonists using the mouse pole test.
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.
Ohno
Yukihiro
Y
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. yohno@gly.oups.ac.jp
Shimizu
Saki
S
Imaki
Junta
J
Ishihara
Shizuka
S
Sofue
Nobumasa
N
Sasa
Masashi
M
Kawai
Yoshiko
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000627:therapeutic use*; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D006220:Haloperidol / Q000633:toxicity; D018476:Hypokinesia / Q000139:chemically induced / Q000188:drug therapy*; D054833:Isoindoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014282:Trihexyphenidyl / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D054833:Isoindoles; D018727:Muscarinic Antagonists; D010879:Piperazines; D011743:Pyrimidines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; C055267:tandospirone; D012701:Serotonin; D014282:Trihexyphenidyl; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D010134:Fenclonine