Effects of tandospirone, a 5-HT1A agonistic anxiolytic agent, on haloperidol-induced catalepsy and forebrain Fos expression in mice.
We studied the effects of tandospirone, a 5-HT(1A) agonistic anxiolytic agent, on haloperidol-induced catalepsy and forebrain Fos expression in mice. Haloperidol (0.5 mg/kg, i.p.) markedly increased the catalepsy time and enhanced Fos expression in the shell (AcS) and core (AcC) regions of the nucleus accumbens, the dorsolateral striatum (dlST), and the lateral septal nucleus (LSN). Tandospirone (0.1 - 1 mg/kg, s.c.) significantly alleviated haloperidol-induced catalepsy in a dose-dependent manner, which was antagonized by WAY-100135 (a selective 5-HT(1A) antagonist). The anticataleptic dose of tandospirone (1 mg/kg, s.c.) significantly reduced haloperidol-induced Fos expression in the dlST. This inhibition by tandospirone was regionally specific, and it failed to affect haloperidol-induced Fos expression either in the AcS, AcC, or LSN. In addition, the reversal of haloperidol-induced striatal Fos expression by tandospirone was antagonized by WAY-100135. These results support the notion that stimulation of 5-HT(1A) receptors region-specifically counteracts the D(2)-blocking actions of haloperidol in the striatum, which may account for the ameliorative effects of 5-HT(1A) agonists on antipsychotic-associated extrapyramidal disorders.
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan. yohno@gly.oups.ac.jp
Yukihiro
Y
Ohno
Saki
S
Shimizu
Junta
J
Imaki
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000633:toxicity*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016762:Genes, fos / Q000187:drug effects*; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007150:Immunohistochemistry; D054833:Isoindoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; C055267:tandospirone; D006220:Haloperidol