Chronic treatment with tandospirone, a serotonin 1A receptor partial agonist, inhibits psychosocial stress-induced changes in hippocampal neurogenesis and behavior

Abstract

Background: The 5-hydroxytryptamine (5-HT) 1A receptors are considered a potential target for the treatment of mental and neuropsychiatric disorders. Several studies have indicated that 5-HT1A receptor agonists increase hippocampal neurogenesis, which is implicated in the action mechanism of antidepressants. However, these agents have not been applied to humans due to intolerable side effects. We recently showed that chronic administration of tandospirone, a clinically available 5-HT1A receptor partial agonist, increased hippocampal neurogenesis dose-dependently. The present study was done to determine if chronic tandospirone treatment has antidepressant potential from the standpoint of hippocampal neurogenesis and behavior.

Methods: Male Sprague-Dawley rats were intraperitoneally administered a vehicle or tandospirone (10mg/kg) once daily for 28 days. Two weeks after starting the injections, animals were exposed to intermittent social defeat (four times over two weeks). The effects of stress and tandospirone on the rodents׳ behavior were evaluated by the Novelty-Suppressed Feeding (NSF) test. The quantification of hippocampal neurogenesis was estimated using immunostaining with Ki-67 and doublecortin (DCX).

Results: Chronic tandospirone treatment reversed the psychosocial stress-induced increase in the latency in the NSF test and decrease in the density of DCX-positive cells in the dentate gyrus of the dorsal and ventral hippocampus. However, no difference in the density of Ki-67-positive cells was observed between the vehicle- and tandospirone-administered groups.

Limitations: To clarify the antidepressant potential of TDS, the other behavioral tests for depression will be required.

Conclusions: Our findings suggest that tandospirone has antidepressant potential through an inhibiting effect on stress-induced changes in hippocampal neurogenesis.

Keywords: Antidepressant; Hippocampal neurogenesis; Novelty-Suppressed Feeding test; Serotonin 1A receptor partial agonist; Social defeat; Tandospirone.