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

Overview

Journal Front Behav Neurosci

Specialty Psychology

Date 2014 Sep 19

PMID 25232308

Citations 7

Authors

Takashi Uehara

Tadasu Matsuoka

Tomiki Sumiyoshi

Affiliations

Soon will be listed here.

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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