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A developmentally regulated and psychostimulant-inducible novel rat gene mrt1 encoding PDZ-PX proteins isolated in the neocortex

Molecular Psychiatry volume 8, pages 434–444 (2003)Cite this article

Abstract

Single or repeated exposure to psychostimulants such as amphetamines and cocaine after postnatal week 3 leads to an enduring enhancement in the psychotomimetic responses elicited by a subsequent challenge of a stimulant in rodents. This behavioral sensitization phenomenon has been considered to be the neural consequences of stimulant-induced alterations in gene expression in the brain after a critical period of postnatal development. Using a differential cloning technique, RNA arbitrarily primed PCR, we have now identified from the rat neocortex a novel and developmentally regulated methamphetamine (MAP)-inducible gene mrt1 (MAP responsive transcript 1). mrt1 encodes two major types of PDZ- and PX-domains containing proteins of approximately 62 kDa in size with different carboxy termini, Mrt1a and Mrt1b. The mrt1 mRNAs for Mrt1a, mrt1a, and for Mrt1b, mrt1b, are predominantly expressed in various brain regions and the testes, respectively. Acute MAP injection upregulated mrt1b expression in the neocortex after postnatal week 3 in a D1 receptor antagonist-sensitive manner without affecting mrt1a expression. This upregulation was mimicked by another stimulant, cocaine, whereas pentobarbital and D1 antagonist failed to change the mrt1b transcript levels. Moreover, repeated daily treatment of MAP, but not MAP plus D1 antagonist, for 5 days caused an augmentation of the basal expression of mrt1b 2 and 3 weeks after the drug discontinuation. These late-developing, cocaine-crossreactive, D1 antagonist-sensitive and long-term regulations of mrt1b by MAP are similar to the pharmacological profiles of stimulant-induced behavioral sensitization, and therefore may be associated with the initiation and/or maintenance of the long-term neuronal adaptation.

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Acknowledgements

We thank Ms M Asakawa and M Kurita for their excellent assistance. This work was partly supported by research grants from the Ministry of Health and Wealth, Japan, the Ministry of Education, Science and Culture, Japan, and the Social Insurance Agency Contract Fund Commissioned to the Japan Health Sciences Foundation.

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Author notes

  1. Y Kajii

    Present address: Research Laboratory I (CNS), Pharmaceuticals Research Division, Mitsubishi Pharma Co., 7-25 Koyata 3, Iruma, Saitama, 358-0026, Japan

Authors and Affiliations

  1. Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

    Y Kajii, S Muraoka, S Hiraoka, K Fujiyama, A Umino & T Nishikawa

  2. Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan

    Y Kajii, S Muraoka, A Umino & T Nishikawa

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  1. Y Kajii
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Correspondence to T Nishikawa.

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Kajii, Y., Muraoka, S., Hiraoka, S. et al. A developmentally regulated and psychostimulant-inducible novel rat gene mrt1 encoding PDZ-PX proteins isolated in the neocortex. Mol Psychiatry 8, 434–444 (2003). https://doi.org/10.1038/sj.mp.4001258

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