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The Journal of Neuroscience, July 11, 2007, 27(28):7604-7615; doi:10.1523/JNEUROSCI.1575-07.2007

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Behavioral/Systems/Cognitive
A Novel Molecule "Shati" Is Involved in Methamphetamine-Induced Hyperlocomotion, Sensitization, and Conditioned Place Preference

Minae Niwa,^1,3 Atsumi Nitta,¹ Hiroyuki Mizoguchi,¹ Yasutomo Ito,² Yukihiro Noda,¹ Taku Nagai,¹ and Toshitaka Nabeshima^1,3

¹Department of Neuropsychopharmacology and Hospital Pharmacy and ²Equipment Center for Research and Education, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan, and ³Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, Nagoya 468-8503, Japan

Correspondence should be addressed to Dr. Toshitaka Nabeshima, Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan. Email: tnabeshi{at}ccmfs.meijo-u.ac.jp

Drug addiction places an enormous burden on society through its repercussions on crime rate and healthcare. Repeated exposure to drugs of abuse causes cellular adaptations in specific neuronal populations that ultimately can lead to a state of addiction. In the present study, we have identified a novel molecule "shati" from the nucleus accumbens (NAc) of mice treated with methamphetamine (METH) using the PCR-select complementary DNA subtraction method. Moreover, we investigated whether shati is involved in METH-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). METH induced expression of shati mRNA dose dependently via dopamine (DA) receptors. We prepared antibodies against shati and, using them, found shati to be expressed in neuronal cells of the mouse brain. Treatment with the shati antisense oligonucleotide (shati-AS), which significantly inhibited the expression of shati mRNA, enhanced the acute METH response, METH-induced behavioral sensitization, and CPP. Blockage of shati mRNA by shati-AS potentiated the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in synaptosomal and vesicular DA uptake in the midbrain. These results suggest that a novel molecule shati is involved in the development of METH-induced hyperlocomotion, sensitization, and CPP. The functional roles of shati in METH-regulated behavioral alternations are likely to be mediated by its inhibitory effects on the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in DA uptake in the midbrain.

Key words: shati; methamphetamine; behavioral sensitization; conditioned place preference; dopamine; addiction

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Received Dec. 18, 2006; revised May 21, 2007; accepted May 21, 2007.

Correspondence should be addressed to Dr. Toshitaka Nabeshima, Department of Chemical Pharmacology, Meijo University Graduate School of Pharmaceutical Sciences, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan. Email: tnabeshi{at}ccmfs.meijo-u.ac.jp

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