Lactate Metabolism as a New Target for the Therapeutics of Schizophrenia
Pp. 135-148 (14)
Takashi Uehara and Tomiki Sumiyoshi
Accumulated evidence indicates that lactate plays a significant role in energy
production in the brain, especially during acute neural activation. The astrocyte-neuron
lactate shuttle hypothesis has been proposed to explain how lactate is supplied to neurons.
Furthermore, the ability of lactate to protect neurons against excite toxicity and oxidative
stress has been reported. There is a growing interest in the role for serotonin (5-HT)1A
receptors in the treatment of negative symptoms and cognitive disturbances of
schizophrenia. This is based on clinical evidence that 5-HT1A agonists, such as
tandospirone, perospirone, and lurasidone, improve cognitive function in patients with
the illness. Data from rodent studies also support the hypothesis that stimulation of
5-HT1Areceptors is advantageous in treating cognitive deficits of schizophrenia.
Rats experiencing transient N-methyl-D-aspartate receptor (NMDA-R) blockade during
the neonatal stage show reduction of the stress-induced increase in extracellular lactate
concentrations in the medial prefrontal cortex around the pubertal period. Treatment with
5-HT1A receptor agonists, such as tandospirone, reversed the decreased lactate production
in these model animals. These observations indicate that lactate metabolism provides a
novel probe for the development of psychotropic compounds to treat core symptoms of
Lactate, energy metabolism, cognition, neuroprotection, 5-HT1A
Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, 2630 Sugitani, 930-0194 Toyama, Japan.