Establishment of dyskinesia, one of the symptoms (side effects) induced by levodopa was assessed in a unilateral 6-OHDA injection rat model. Since it has become clear that serotonin system has an important role in this rat model (levodopa-induced dyskinesia [LID] rats), a serotonergic agonist for inhibiting dyskinesia-like symptom was also assessed.
AIMs scores (locomotive, limb, axial, orolingual, and total) were high in the LID rats. Repeatedly administered tandospirone for 14 days also decreased AIMs scores (limb, axial, orolingual, and total) significantly; the reactivity was dose-dependent. The following findings were also noted in the LID rats: decreases in the contents of DA, DOPAC, HVA, 5-HT, and glutamate and DOPAC/DA and glutamate/GABA ratios in the striatum; decreases in DOPAC/DA and HVA/DA ratios, and an increase in glutamate/GABA ratio in the hypothalamus. Changes in the contents and ratios in the hypothalamus were improved by 14-day repeated administration of tandospirone.
As described above, tandospirone decreased AIMs scores without affecting rotational behavior induced by L-dopa administration in LID rats and inhibited development of side effects. The possibility is suggested that the inhibiting action occurs through at least the hypothalamus.