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Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons

Author

Listed:
  • Mark A. Ungless

    (Ernest Gallo Clinic and Research Center, University of California)

  • Jennifer L. Whistler

    (Ernest Gallo Clinic and Research Center, University of California)

  • Robert C. Malenka

    (Nancy Pritzker Laboratory, Stanford University School of Medicine)

  • Antonello Bonci

    (Ernest Gallo Clinic and Research Center, University of California)

Abstract

How do drugs of abuse modify neural circuitry and thereby lead to addictive behaviour? As for many forms of experience-dependent plasticity, modifications in glutamatergic synaptic transmission have been suggested to be particularly important1,2,3,4. Evidence of such changes in response to in vivo administration of drugs of abuse is lacking, however. Here we show that a single in vivo exposure to cocaine induces long-term potentiation of AMPA (α-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated currents at excitatory synapses onto dopamine cells in the ventral tegmental area. Potentiation is still observed 5 but not 10 days after cocaine exposure and is blocked when an NMDA (N-methyl-d-aspartate) receptor antagonist is administered with cocaine. Furthermore, long-term potentiation at these synapses is occluded and long-term depression is enhanced by in vivo cocaine exposure. These results show that a prominent form of synaptic plasticity can be elicited by a single in vivo exposure to cocaine and therefore may be involved in the early stages of the development of drug addiction.

Suggested Citation

  • Mark A. Ungless & Jennifer L. Whistler & Robert C. Malenka & Antonello Bonci, 2001. "Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons," Nature, Nature, vol. 411(6837), pages 583-587, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6837:d:10.1038_35079077
    DOI: 10.1038/35079077
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    Cited by:

    1. In Bum Lee & Eugene Lee & Na-Eun Han & Marko Slavuj & Jeong Wook Hwang & Ahrim Lee & Taeyoung Sun & Yehwan Jeong & Ja-Hyun Baik & Jae-Yong Park & Se-Young Choi & Jeehyun Kwag & Bong-June Yoon, 2024. "Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Himanshu Gangal & Xueyi Xie & Zhenbo Huang & Yifeng Cheng & Xuehua Wang & Jiayi Lu & Xiaowen Zhuang & Amanda Essoh & Yufei Huang & Ruifeng Chen & Laura N. Smith & Rachel J. Smith & Jun Wang, 2023. "Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Allen P. F. Chen & Lu Chen & Kaiyo W. Shi & Eileen Cheng & Shaoyu Ge & Qiaojie Xiong, 2023. "Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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