Neuron: Scientists Reveal the Neural Circuits That Smoking Promotes Anxiety

Nicotine is a highly addictive substance that naturally exists in tobacco

The ventral tegmental area (VTA) of the midbrain is part of the two main dopamine nerve pathways in the brain

On July 10, 2021, French scientist Philippe Faure published an article in Neuron, revealing that nicotine inhibits the dopamine neural circuit that VTA projects to the amygdala and promotes anxiety

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, and partially activated or inhibited DA neurons, which are called nicotine-activated neurons and inhibitory neurons

Virus tracer traces the neural circuits activated and inhibited by nicotine

Subsequently, retrograde tracer virus was injected into the NAc brain area and the amygdala brain area, and it was found that 93% of the nicotine-activated neurons projected to the NAc brain area (VTA-NAc), and 86% of the nicotine-inhibited neurons projected to the amygdala (VTA).

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.

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

Nicotine causes anxiety-like behavior

Researchers found that after intraperitoneal injection of nicotine (0.

In β2 type nAChR knockout mice, nicotine does not cause DA neurons in the VTA brain area to activate or inhibit the 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

The researchers next explored the behavioral effects of the two neural circuits of VTA-NAc and VTA-Amg

Neither photo-activation nor photo-inhibition of the VTA-NAc loop will affect anxiety behavior, but activation of the loop causes conditional position preference

The mice did not exhibit anxiety-like behaviors after light-activating the VTA-Amg neural circuit while injecting nicotine into the intraperitoneal cavity

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

Original source:

Claire Nguyen, et al.