AUTHOR=Uehara Takashi , Matsuoka Tadasu , Sumiyoshi Tomiki 

TITLE=Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2014.00291

DOI=10.3389/fnbeh.2014.00291

ISSN=1662-5153

ABSTRACT=<p><bold>Rationale:</bold> Augmentation therapy with serotonin-1A (5-HT<sub>1A</sub>) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production.</p><p><bold>Objectives and methods:</bold> The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia.</p><p><bold>Results:</bold> Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment.</p><p><bold>Conclusions:</bold> These results suggest that stimulation of 5-HT<sub>1A</sub> receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT<sub>1A</sub> agonism improve cognitive impairment of schizophrenia and related disorders.</p>