Are D-Neurons and Trace Amine-Associated Receptor, Type 1 Involved in Mesolimbic Dopamine Hyperactivity of Schizophrenia?Keiko Ikemoto*
Department of Psychiatry, Iwaki Kyoritsu General Hospital, Iwaki 973-8555, Japan
- *Corresponding Author:
- Keiko Ikemoto, MD, PhD
Department of Neuropsychiatry
Fukushima Medical University
School of Medicine, 1 Hikarigaoka
Fukushima 960- 1295, Japan
E-mail: [email protected]
Received date: February 24, 2012; Accepted date: March 21, 2012; Published date: March 22, 2012
Citation: Ikemoto K (2012) Are D-Neurons and Trace Amine-Associated Receptor, Type 1 Involved in Mesolimbic Dopamine Hyperactivity of Schizophrenia? Med chem 2:038-040. doi:10.4172/2161-0444.1000111
Copyright: © 2012 Ikemoto K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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, has a large number of ligands, including tyramine, β-phenylethylamine and methamphetamine that influence on human mental state, and is now regarded as a target 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 author and her colleagues reported the decrease of D-neurons in the striatum and nucleus accumbens of postmortem brains of patients with schizophrenia. This may imply 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, may explain mesolimbic DA hyperactivity of schizophrenia.