Neuron: Scientists Reveal the Neural Circuits That Smoking Promotes Anxiety

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Nicotine is a highly addictive substance that naturally exists in tobacco
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Addictive drugs such as nicotine are thought to "hijack" the mechanism of reinforcement learning: step down on the reward effect of the normal state and increase the reward effect on the drug
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This abnormal reinforcement learning process is thought to be the basis of drug addiction
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The ventral tegmental area (VTA) of the midbrain is part of the two main dopamine nerve pathways in the brain
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Nicotine exerts its effect by directly activating the nicotinic acetylcholine receptor (nAChR) expressed on midbrain dopamine (DA) and GABA neurons
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On July 10, 2021, French scientist Philippe Faure published an article in Neuron, revealing that nicotine inhibits the dopamine circuit that VTA projects to the amygdala and promotes anxiety
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Nicotine activates or inhibits dopamine neurons in the VTA brain area.
After the researchers injected nicotine intravenously, electrophysiological experiments found that the firing frequency of DA neurons in the VTA brain area increased, or decreased, partially activated or inhibited DA neurons, called nicotine-activated neurons And inhibit neurons
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Virus tracing traces the neural circuits activated and inhibited by nicotine and then injects retrograde tracer virus into the NAc brain area and the amygdala brain area respectively.
It was found that 93% of nicotine-activated neurons projected to the NAc brain area (VTA-NAc), 86 % Nicotine-inhibited neurons project to the amygdala (VTA-Amg)
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In this way, an activated VTA-NAc loop and an inhibited VTA-Amg loop are formed
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In order to further confirm the specific VTA-NAc and VTA-Amg loops of nicotine, they injected DA fluorescent receptors of viral vectors into the brain regions of NAc and Amg.
After the tail vein injection of nicotine, the release of DA in the brain of NAc increased, and the release of DA in the brain of Amg decreased
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These results confirm that nicotine can drive opposite functional responses in the two different DA loops of VTA
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The previous nicotine relied on the dopamine (DA) system in the VTA brain area to produce a reward effect, and it also produced a negative effect on anxiety and stress-related depression-like behaviors
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Nicotine induces anxiety-like behaviors.
Researchers have found that after intraperitoneal injection of nicotine (0.
5mg/kg), mice showed obvious anxiety-like behaviors in O-maze and open field behaviors
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Injecting nicotine specifically into the VTA brain area, the mice will also show anxiety-like behavior
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In β2 type nAChR knockout mice, nicotine does not cause DA neurons in the VTA brain area to activate or inhibit response, and there is no anxiety-like behavior; however, when β2 type nAChR is specifically expressed in the VTA region, nicotine can exert the above Effect
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The researchers next explored the behavioral effects of the two neural circuits of VTA-NAc and VTA-Amg
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Photoinhibition of the VTA-Amg loop induces anxiety-like behavior, and the activation of this neural loop exerts an anxiolytic effect, but does not cause conditional position preference
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Neither photo-activation nor photo-inhibition of the VTA-NAc loop will affect anxiety behavior, but activation of the loop causes conditional position preference
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The mice did not exhibit anxiety-like behaviors after light-activating the VTA-Amg neural circuit while injecting nicotine into the intraperitoneal cavity
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It shows that activating this neural circuit can block the negative emotional behavior of nicotine
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In summary, this article uses nicotine to induce two different neuronal responses in the VTA brain area, and discovers the VTA-NAc activation loop and the VTA-Amg inhibitory loop
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These two loops perform their own duties: the activation loop participates in reward-motivated behaviors, and the inhibition loop participates in negative emotion (anxiety) behaviors
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[References] 1.
https://doi.
org/10.
1016/j.
neuron.
2021.
06.
013 The pictures in the article are all from the reference original download link: https://pan.
baidu.
com/s/1jtH55vaeF2QS4lgvtDK96g Extraction code: irhb