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Conditional Knockout of NMDA Receptors in Dopamine Neurons Prevents Nicotine-Conditioned Place Preference

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  • Lei Phillip Wang
  • Fei Li
  • Xiaoming Shen
  • Joe Z Tsien

Abstract

Nicotine from smoking tobacco produces one of the most common forms of addictive behavior and has major societal and health consequences. It is known that nicotine triggers tobacco addiction by activating nicotine acetylcholine receptors (nAChRs) in the midbrain dopaminergic reward system, primarily via the ventral tegmental area. Heterogeneity of cell populations in the region has made it difficult for pharmacology-based analyses to precisely assess the functional significance of glutamatergic inputs to dopamine neurons in nicotine addiction. By generating dopamine neuron-specific NR1 knockout mice using cre/loxP-mediated method, we demonstrate that genetic inactivation of the NMDA receptors in ventral tegmental area dopamine neurons selectively prevents nicotine-conditioned place preference. Interestingly, the mutant mice exhibit normal performances in the conditioned place aversion induced by aversive air puffs. Therefore, this selective effect on addictive drug-induced reinforcement behavior suggests that NMDA receptors in the dopamine neurons are critical for the development of nicotine addiction.

Suggested Citation

  • Lei Phillip Wang & Fei Li & Xiaoming Shen & Joe Z Tsien, 2010. "Conditional Knockout of NMDA Receptors in Dopamine Neurons Prevents Nicotine-Conditioned Place Preference," PLOS ONE, Public Library of Science, vol. 5(1), pages 1-7, January.
  • Handle: RePEc:plo:pone00:0008616
    DOI: 10.1371/journal.pone.0008616
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    References listed on IDEAS

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    1. Ya-Ping Tang & Eiji Shimizu & Gilles R. Dube & Claire Rampon & Geoffrey A. Kerchner & Min Zhuo & Guosong Liu & Joe Z. Tsien, 1999. "Genetic enhancement of learning and memory in mice," Nature, Nature, vol. 401(6748), pages 63-69, September.
    2. Volodymyr I. Pidoplichko & Mariella DeBiasi & John T. Williams & John A. Dani, 1997. "Nicotine activates and desensitizes midbrain dopamine neurons," Nature, Nature, vol. 390(6658), pages 401-404, November.
    3. Masayuki Matsumoto & Okihide Hikosaka, 2009. "Two types of dopamine neuron distinctly convey positive and negative motivational signals," Nature, Nature, vol. 459(7248), pages 837-841, June.
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