Effects of sarizotan on the corticostriatal glutamate pathways

The effects of sarizotan, a 5-HT1A agonist with additional affinity for D-3 and D-4 receptors, have been studied on the corticostriatal glutamate pathways using dual-probe microdialysis in the awake rat. Sarizotan given systemically (0.1-10 mg/kg s.c.) or perfused into the motor cortex (10 mu M) produced 20-30% reduction of cortical and striatal glutamate levels. The inhibitory effects of the systemic sarizotan on cortical and striatal glutamate levels were counteracted by intracortical perfusion with the 5-HT1A antagonist WAY100135 (10 mu M). These findings suggest that the anti-dyskinetic properties of sarizotan could be mediated via its 5-HT1A agonist actions in the motor cortex, leading to reduced activity in the corticostriatal glutamate pathways with reduced activation of the striatopallidal GABA pathway mediating motor inhibition.