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.
abstract: BACKGROUND
  Augmentation therapy with serotonin-1A (5-HT1A) 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.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest that stimulation of 5-HT1A 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-HT1A agonism improve cognitive impairment of schizophrenia and related disorders.
authors.affiliation: Department of Neuropsychiatry, Kanazawa Medical University, Ucninada-cho Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Psychiatry, Matsuoka Hospital Oyabe, Toyama, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Matsuoka
authors.affiliation: Department of Clinical Research Promotion, National Center Hospital, National Center of Neurology and Psychiatry Tokyo, Japan.
authors.forename: Tomiki
authors.initials: T
authors.lastname: Sumiyoshi
keywords: 5-HT1A; NMDA receptor; animal model; cognition; glutamate; lactate; microdialysis; schizophrenia