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Subsecond dopamine release promotes cocaine seeking

Author

Listed:
  • Paul E. M. Phillips
  • Garret D. Stuber

    (University of North Carolina)

  • Michael L. A. V. Heien
  • R. Mark Wightman

    (University of North Carolina)

  • Regina M. Carelli

    (University of North Carolina)

Abstract

The dopamine-containing projection from the ventral tegmental area of the midbrain to the nucleus accumbens is critically involved in mediating the reinforcing properties of cocaine1,2. Although neurons in this area respond to rewards on a subsecond timescale3,4, neurochemical studies have only addressed the role of dopamine in drug addiction by examining changes in the tonic (minute-to-minute) levels of extracellular dopamine5,6,7,8,9. To investigate the role of phasic (subsecond) dopamine signalling10, we measured dopamine every 100 ms in the nucleus accumbens using electrochemical technology11. Rapid changes in extracellular dopamine concentration were observed at key aspects of drug-taking behaviour in rats. Before lever presses for cocaine, there was an increase in dopamine that coincided with the initiation of drug-seeking behaviours. Notably, these behaviours could be reproduced by electrically evoking dopamine release on this timescale. After lever presses, there were further increases in dopamine concentration at the concurrent presentation of cocaine-related cues. These cues alone also elicited similar, rapid dopamine signalling, but only in animals where they had previously been paired to cocaine delivery. These findings reveal an unprecedented role for dopamine in the regulation of drug taking in real time.

Suggested Citation

  • Paul E. M. Phillips & Garret D. Stuber & Michael L. A. V. Heien & R. Mark Wightman & Regina M. Carelli, 2003. "Subsecond dopamine release promotes cocaine seeking," Nature, Nature, vol. 422(6932), pages 614-618, April.
    • Handle: RePEc:nat:nature:v:422:y:2003:i:6932:d:10.1038_nature01476
    DOI: 10.1038/nature01476
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    Cited by:

    1. Ayaka Kato & Kenji Morita, 2016. "Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation," PLOS Computational Biology, Public Library of Science, vol. 12(10), pages 1-41, October.
    2. Miguel Á. Luján & Dan P. Covey & Reana Young-Morrison & LanYuan Zhang & Andrew Kim & Fiorella Morgado & Sachin Patel & Caroline E. Bass & Carlos Paladini & Joseph F. Cheer, 2023. "Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Min Jung Kim & Daniel J. Gibson & Dan Hu & Tomoko Yoshida & Emily Hueske & Ayano Matsushima & Ara Mahar & Cynthia J. Schofield & Patlapa Sompolpong & Kathy T. Tran & Lin Tian & Ann M. Graybiel, 2024. "Dopamine release plateau and outcome signals in dorsal striatum contrast with classic reinforcement learning formulations," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Yu-Hsuan Lin & Kuan-I Lin & Yuan-Chien Pan & Sheng-Hsuan Lin, 2020. "Investigation of the Role of Anxiety and Depression on the Formation of Phantom Vibration and Ringing Syndrome Caused by Working Stress during Medical Internship," IJERPH, MDPI, vol. 17(20), pages 1-10, October.
    5. Seth R. Batten & Dan Bang & Brian H. Kopell & Arianna N. Davis & Matthew Heflin & Qixiu Fu & Ofer Perl & Kimia Ziafat & Alice Hashemi & Ignacio Saez & Leonardo S. Barbosa & Thomas Twomey & Terry Lohre, 2024. "Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange," Nature Human Behaviour, Nature, vol. 8(4), pages 718-728, April.

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