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-HT1A 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-HT1A 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-HT1A receptors region-specifically counteracts the D2-blocking actions of haloperidol in the striatum, which may account for the ameliorative effects of 5-HT1A agonists on antipsychotic-associated extrapyramidal disorders.