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.

Department of Brain Pathophysiology and Biochemistry Prague Psychiatric Centre Prague Czech Republic

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