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Cell Discov. 2018 Nov 6;4:60. doi: 10.1038/s41421-018-0060-z. eCollection 2018.

Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA.

Wei C#1,2,3, Han X#4, Weng D3, Feng Q3, Qi X3, Li J4, Luo M3,5.

Author information

1
1School of Life Sciences, Peking University, Beijing, 100871 China.
2
2Peking University-Tsinghua University-NIBS Graduate Program, Peking University, Beijing, 100081 China.
3
3National Institute of Biological Sciences (NIBS), Beijing, 102206 China.
4
4Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850 China.
5
5School of Life Sciences, Tsinghua University, Beijing, 100084 China.
#
Contributed equally

Abstract

Heroin, nicotine, cocaine, and MDMA are abused by billions of people. They are believed to target midbrain dopamine neurons and/or serotonin neurons, but their effects on the dynamic neuronal activity remain unclear in behaving states. By combining cell-type-specific fiber photometry of Ca2+ signals and intravenous drug infusion, here we show that these four drugs of abuse profoundly modulate the activity of mouse midbrain dopamine neurons and serotonin neurons with distinct potency and kinetics. Heroin strongly activates dopamine neurons, and only excites serotonin neurons at higher doses. Nicotine activates dopamine neurons in merely a few seconds, but produces minimal effects on serotonin neurons. Cocaine and MDMA cause long-lasting suppression of both dopamine neurons and serotonin neurons, although MDMA inhibits serotonin neurons more profoundly. Moreover, these inhibitory effects are mediated through the activity of dopamine and serotonin autoreceptors. These results suggest that the activity of dopamine neurons and that of serotonin neurons are more closely associated with the drug's reinforcing property and the drug's euphorigenic property, respectively. This study also shows that our methodology may facilitate further in-vivo interrogation of neural dynamics using animal models of drug addiction.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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