Although dopamine (DA) dysfunction is a well-known hypothesis for etiology of schizophrenia, molecular basis of mesolimbic DA hyperactivity has not yet been clarified. To explain this, modulating function of trace amines on DA neurotransmission and the decreased number of striatal D-neurons, trace amine-producing neurons, were considered. Notably, Trace Amine-Associated Receptor, Type 1 (TAAR1), a subtype of trace amine receptors, with a large number of ligands, including tyramine, ?-phenylethylamine and methamphetamine that have influence on human mental state, is now regarded as a targeted receptor for novel neuroleptics. Reduced stimulation of TAAR1 on DA neurons in the midbrain ventral tegmental area (VTA) has been revealed to increase firing frequency of VTA DA neurons. The decrease of D-neurons in the striatum and nucleus accumbens of postmortem brains of patients with schizophrenia has been reported. This implies the decrease of trace amine synthesis and consequent reduction of the stimulation of TAAR1 on terminals of midbrain VTA DA neurons, and may lead to mesolimbic DA hyperactivity in schizophrenia. The decrease of striatal D-neurons of postmortem brains of schizophrenia might be due to neural stem cell dysfunction in the subventricular zone of lateral ventricle. The new “D-cell hypothesis”, in which D-neurons and TAAR1 are involved, is in agreement with recent reports of TAAR1 research using animal models.

Author Name: Keiko Ikemoto

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Keywords: Dopamine, D-neuron, Trace Amine, Schizophrenia, TAAR1

ISSN: 2326-4705

EISSN: 2326-473X

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