Proteomic analysis of nicotine-associated protein expression in the striatum of repeated nicotine-treated rats

https://doi.org/10.1016/j.bbrc.2004.11.034Get rights and content

Abstract

Through the proteomic analysis using 2-dimensional electrophoresis, the nicotine addiction-associated proteins were extensively screened in the striatum of rat brains. The nicotine addiction was developed by repeated nicotine injection (0.4 mg/kg s.c.), twice daily for 7 days, followed by one challenge injection after a 3 day withdrawal period, and then confirmed by observing a 2.3-fold increase in locomoter activity. The 3 up- and 4 down-regulated proteins were selected and identified to be zinc-finger binding protein-89 (ZBP-89), 2′3′-cyclic nucleotide 3′-phosphodiesterase 1, deoxyribonuclease 1-like 3 (DNase1l3), tandem pore domain halothane inhibited K+ channel (THIK-2), brain-specific hyaluronan-binding protein (BRAL-1), death effector domain-containing DNA binding protein (DEDD), and brain-derived neurotrophic factor (BDNF) by mass spectrophotometric fingerprinting. Among them, the expression patterns of ZEB-89, DNase1l3, THIK-2, DEDD, and BDNF mRNAs were found to be coincident with those of cognate proteins, by using RT-PCR analysis. These proteins could be suggested as drug targets to develop a new therapy for nicotine-associated diseases, as well as the clues to understand the mechanism of nicotine.

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Materials and methods

Animals and nicotine treatment. Male Sprague–Dawley rats weighing 250–280 g at the start of experiments were used throughout. Prior to the experimental manipulation, the animals were given a period of 1 week to adjust to the new environment. Animals were cared for and handled in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. Animals were divided randomly into nicotine-treated (NIC, n = 10) and control (CONT, n = 10) groups. For nicotine

Results and discussion

Tobacco smoking still remains a major health problem worldwide. Nicotine is a principal component of tobacco, eliciting addictive behavior in human [1], [5], [6]. Intermittent nicotine administration brings about the behavioral sensitization, which is defined as an increased behavioral and/or neurochemical response [8]. Locomotor activation and reinforcement may be relevant to the stimulatory effects of nicotine on the mesolimbic dopaminergic system [18]. The striatum and nucleus accumbens are

Acknowledgments

The authors thank Prof. Kang-Duk Choi at Hankyong National University for the technical support and the helpful discussion. This study was supported by the Brain Korea 21 Project from the Ministry of Education, Republic of Korea.

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