Serotonin-1A Receptors and Cognitive Enhancement in Schizophrenia: Role for Brain Energy Metabolism

Sumiyoshi, Tomiki; Uehara, Takashi

doi:10.5772/36118

Cited by 1 publication

(3 citation statements)

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“…Our investigation revealed that the acute administration of tandospirone increased eLAC in the medial prefrontal cortex (mPFC) of naïve adult rats [ 63 ], while chronic treatment ameliorated abnormal lactate metabolism in the mPFC of a rat model of schizophrenia [ 64 , 65 ]. These data on brain energy metabolism support the hypothesis that 5-HT 1A agonism can improve cognitive deficits of schizophrenia [ 55 , 66 ].…”

Section: -Ht 1a Agonists In the Treatment Of Cognsupporting

confidence: 77%

“…Furthermore, in a randomized, double-blind, placebo-controlled study, the addition of buspirone (30 mg/kg) outperformed the placebo in improving attention/information processing in patients treated with SGAs, such as olanzapine and risperidone [ 53 ]. These findings provided the basis for the ability of 5-HT 1A receptor stimulation to enhance cognition, a therapeutic approach that has promoted the development of novel antipsychotic drugs [ 48 - 50 , 55 ].…”

Section: -Ht 1a Agonists In the Treatment Of Cognmentioning

confidence: 99%

“…Sumiyoshi et al . postulated a putative neural network involving glutamate, GABA, 5-HT and DA associated with the ability of 5-HT 1A agonists to enhance cognition in schizophrenia [ 50 , 51 , 55 ] Fig. ( 2 ).…”

Section: -Ht 1a Agonists In the Treatment Of Cognmentioning

confidence: 99%

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New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function

Uehara

Sumiyoshi²,

Kurachi³

2015

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Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.

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