Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia.

Tetrahydrobiopterin (BH4) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine (DA) and serotonin (5-HT) as well as the release of glutamate (Glu). Deficiencies in BH4 levels and reduced activities of BH(4)-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by BH(4) may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in BH(4) by knocking out the expression of a functional sepiapterin reductase gene (spr -/-) has added new insights into the potential role of BH(4) in the pathophysiology and improved treatment of schizophrenia.