Chronic treatment with tandospirone, a 5-HT(1A) receptor partial agonist, suppresses footshock stress-induced lactate production in the prefrontal cortex of rats

Serotonin 1A receptor (5-HT1A-R) agonists have been demonstrated to elicit antidepressant and anxiolytic effects. Lactate has been considered to play a major role in energy metabolism in the brain. Specifically, extracellular lactate concentrations (eLAC) have been suggested to reflect neural activity. Mild physical (e.g., handling) and non-physical (e.g., psychological) stressors have been shown to increase eLAC in several brain regions, including the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). Using in vivo microdialysis technique, we measured eLAC in the mPFC and BLA of rats under electric footshock stress to clarify the effect of repeated injection procedure (saline, once daily for 14 days) as a stressor on brain energy metabolism. Then, we examined the effect of chronic treatment with tandospirone, a 5-HT1A-R partial agonist, on eLAC during footshock stress in the mPFC. Footshock stress led to an increase in eLAC both in the mPFC and BLA in rats without injections. Repeated saline injection increased basal eLAC in the BLA, while footshock-induced lactate increment was reduced. In the mPFC, repeated saline injection did not affect basal eLAC and footshock-induced eLAC increments. Chronic treatment with tandospirone, at 0.2 and 1.0 mg/kg/day, but not 2.0 mg/kg/day, attenuated footshock stress-induced eLAC elevation in the mPFC. These observations suggest that eLAC in the BLA is sensitive to repeated exposure to physical stress. Data also indicate chronic treatment with tandospirone diminishes acute energy demands during neural activation in the mPFC. The implications of the present findings in relation to clinical efficacy of 5-HT1A agonists are discussed.