Abstract | RATIONALE: 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. OBJECTIVES AND METHODS: 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.
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Authors | Takashi Uehara, Tadasu Matsuoka, Tomiki Sumiyoshi |
Journal | Frontiers in behavioral neuroscience
(Front Behav Neurosci)
Vol. 8
Pg. 291
( 2014)
ISSN: 1662-5153 [Print] Switzerland |
PMID | 25232308
(Publication Type: Journal Article)
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