Lactate Metabolism as a New Target for the Therapeutics of Schizophrenia

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-HT_1A 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-HT_1Areceptors 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-HT_1A 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 schizophrenia.

Keywords: Lactate, energy metabolism, cognition, neuroprotection, 5-HT1A receptor, schizophrenia.