Conditional knockout of NMDA receptors in dopamine neurons prevents nicotine-conditioned place preference

Lei Wang, Fei Li, Xiaoming Shen, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere8616
JournalPloS one
Volume5
Issue number1
DOIs
StatePublished - Jan 7 2010

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nicotine
Dopaminergic Neurons
N-Methyl-D-Aspartate Receptors
Nicotine
Neurons
Dopamine
neurons
dopamine
Ventral Tegmental Area
Tobacco
Addictive Behavior
cholinergic receptors
smoking (habit)
mice
Cholinergic Receptors
pharmacology
Population Characteristics
Mesencephalon
Reward
Knockout Mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Conditional knockout of NMDA receptors in dopamine neurons prevents nicotine-conditioned place preference. / Wang, Lei; Li, Fei; Shen, Xiaoming; Tsien, Joseph Zhuo.

In: PloS one, Vol. 5, No. 1, e8616, 07.01.2010.

Research output: Contribution to journalArticle

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