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Subsecond dopamine release promotes cocaine seeking

An Erratum to this article was published on 22 May 2003

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.

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Figure 1: Dopamine release in the nucleus accumbens evoked by a stimulus train (24 pulses, 60 Hz, 120 µA; represented by the grey bar).
Figure 2: Rapid increase in extracellular dopamine in the nucleus accumbens relative to the lever-press response for cocaine.
Figure 3: Rapid increase in extracellular dopamine after probe presentation of cocaine-associated stimuli.
Figure 4: Effect of electrically evoked dopamine release on lever-press responding for cocaine.

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Acknowledgements

We thank M. Roitman, D. Robinson, R. Gainetdinov, P. Garris and S. Grigson for useful comments, and J. Venton, J. Peterson, C. McKinney, S. Brooks and J. Wondolowski for technical assistance. We also acknowledge the vision of R. Adams who set the foundation for this work. This work was supported by grants from the National Institute on Drug Abuse to R.M.W. and R.M.C.

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Correspondence to Regina M. Carelli.

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Phillips, P., Stuber, G., Heien, M. et al. Subsecond dopamine release promotes cocaine seeking. Nature 422, 614–618 (2003). https://doi.org/10.1038/nature01476

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