Rationale: Augmentation therapy with serotonin-1A receptor (5-HT1A) partial agonists has been suggested to ameliorate psychotic symptoms in patients with schizophrenia.
Objective and methods: The objective of the present study was to examine the effect of repeated administration of tandospirone (0.05 and 5 mg/kg) on locomotor activity in a novel environment and on sensorimotor gating in rats treated with the N-methyl-D-aspartate receptor antagonist MK-801, which has been used in animal models of schizophrenia. Furthermore, we sought to determine whether the effect of tandospirone on these behavioural measures is blocked by WAY 100635 (0.3 mg/kg), a 5-HT1A receptor antagonist, and whether there is an interaction between haloperidol (0.1 mg/kg; a dopamine-D2 receptor antagonist) and tandospirone.
Results: Tandospirone at 5 mg/kg, but not 0.05 mg/kg, decreased locomotor activity in saline or MK-801-treated rats, which were not affected by co-treatment with WAY 100635. Haloperidol decreased locomotion both in saline and MK-801-treated animals, and this effect was not evident in the latter group receiving the higher dose of tandospirone. Tandospirone (5 mg/kg)-induced disruption of sensorimotor gating in saline or MK-801-treated animals was reversed by WAY-100635, but not by haloperidol.
Conclusions: These findings suggest that behavioural changes induced by tandospirone are not fully blocked by 5-HT1A antagonists and that tandospirone (5 mg/kg) potentiates the effect of MK-801. Overall, these findings point to an interaction between NMDA and 5-HT(1A) receptors. Part of the effect of tandospirone on locomotor activity may be mediated by the actions of its active metabolites on other neurotransmitter systems.