Summary: A new study reports it may be possible to influence alcohol drinking behavior by activating specific neurons.
Source: Texas A&M.
Activation of D2 neurons could discourage alcoholics from wanting another drink.
By activating particular neurons, we may be able to influence alcohol drinking behavior, according to new findings published by researchers at the Texas A&M Health Science Center College of Medicine in the journal Biological Psychiatry.
The group’s prior research showed that alcohol consumption alters the physical structure and function of neurons, called medium spiny neurons, in the dorsomedial striatum. Essentially, they found that activation of one type of neuron, called D1, determines whether one drink leads to two. Now, they’ve discovered the ones that tell us to stop.
These neurons can be thought of like a tree, with many branches, and many small protrusions, or spines, coming off of them. Each neuron has one of two types of dopamine receptors–D1 or D2–and so can be thought of as either D1 or D2 neurons. D1 neurons are informally called part of a “go” pathway in the brain, while D2 neurons are in the “no-go” pathway. In other words, when D2 neurons are activated, they discourage action–telling you to wait, to stop, to do nothing.
“At least from the addiction point of view, D2 neurons are good,” said Jun Wang, MD, PhD, the corresponding author on the paper and assistant professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M College of Medicine. “When they are activated, they inhibit drinking behavior, and therefore activating them is important for preventing problem drinking behavior.”
The trouble is, even in individuals without alcoholism, D2 neurons tend to become deactivated when we drink too much. This deactivation means there is nothing telling us to stop drinking, so we drink more, in a self-perpetuating cycle.
The researchers found that in animal models, repeated cycles of excessive alcohol intake, followed by abstaining from alcohol, actually changed the strength of these neuronal connections, making D2 signals less powerful–which results in essentially training the individual to seek alcohol. “Think of the binge drinking behavior of so many young adults,” Wang said. “Essentially they are probably doing the same thing that we’ve shown leads to inhibition of these so-called ‘good’ neurons and contributes to greater alcohol consumption.”
These findings provide insight into another mechanism underlying the complicated disease we call alcoholism. “Our current and previous research are essentially two sides of the same coin,” Wang said. “D1 and D2 medium spiny neurons have essentially opposing roles in alcohol consumption.”
By manipulating the activity of these neurons, the researchers were actually able to change the alcohol-drinking behavior of the animal models who had been “trained” to seek alcohol. By activating D2 neurons, they were able to decrease alcohol consumption, and the more the D2 neurons were activated, the greater the effect is likely to be.
Although Wang cautions that we are still a long way from testing this in humans, in theory, if we could someday use drugs or electrical stimulation or some other method of activating the D2 neurons–these so-called “no-go” neurons–then we might be able to prevent alcoholics from wanting another drink. “That’s the ultimate goal,” Wang said. “I hope these findings will eventually be able to be used for treatment for alcohol addiction.”
About this neuroscience research article
Funding: The research was supported in part by a grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Funding also provided by Texas Research Society on Alcoholism.
Source: Holly Shive – Texas A&M Image Source: This NeuroscienceNews.com image is credited to Texas A&M University. Original Research:Abstract for “Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption” by Yifeng Cheng, Cathy C.Y. Huang, Tengfei Ma, Xiaoyan Wei, Xuehua Wang, Jiayi Lu, Jun Wang in Biological Psychiatry. Published online May 27 2016 doi:10.1016/j.biopsych.2016.05.016
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]Texas A&M. “Pinpointing the Neurons That Tell the Brain When to Stop Drinking.” NeuroscienceNews. NeuroscienceNews, 6 July 2016. <https://neurosciencenews.com/d2-neurons-alcohol-consumption-4627/>.[/cbtab][cbtab title=”APA”]Texas A&M. (2016, July 6). Pinpointing the Neurons That Tell the Brain When to Stop Drinking. NeuroscienceNew. Retrieved July 6, 2016 from https://neurosciencenews.com/d2-neurons-alcohol-consumption-4627/[/cbtab][cbtab title=”Chicago”]Texas A&M. “Pinpointing the Neurons That Tell the Brain When to Stop Drinking.” https://neurosciencenews.com/d2-neurons-alcohol-consumption-4627/ (accessed July 6, 2016).[/cbtab][/cbtabs]
Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption
Background Repeated exposure to addictive drugs and alcohol triggers glutamatergic and GABAergic plasticity in many neuronal populations. The dorsomedial striatum (DMS), a brain region critically involved in addiction, contains medium spiny neurons (MSNs) expressing dopamine D1 or D2 receptors, which form direct and indirect pathways, respectively. It is unclear how alcohol-evoked plasticity in the DMS contributes to alcohol consumption in a cell type-specific manner.
Methods Mice were trained to consume alcohol using an intermittent-access two-bottle-choice drinking procedure. Slice electrophysiology was used to measure glutamatergic and GABAergic strength in DMS D1- and D2-MSNs of alcohol-drinking mice and their controls. In vivo chemogenetic and pharmacological approaches were employed to manipulate MSN activity and their consequences on alcohol consumption were measured.
Results Repeated cycles of alcohol consumption and withdrawal in mice strengthened glutamatergic transmission in D1-MSNs and GABAergic transmission in D2-MSNs. In vivo chemogenetic excitation of D1-MSNs, mimicking glutamatergic strengthening, promoted alcohol consumption; the same effect was induced by D2-MSN inhibition, mimicking GABAergic strengthening. Importantly, suppression of GABAergic transmission via D2 receptor-glycogen synthase kinase-3β (GSK3β) signaling dramatically reduced excessive alcohol consumption, as did selective inhibition of D1-MSNs or excitation of D2-MSNs.
Conclusions Our results suggest that repeated cycles of excessive alcohol intake and withdrawal potentiates glutamatergic strength exclusively in D1-MSNs and GABAergic strength specifically in D2-MSNs of the DMS, which concurrently contribute to alcohol consumption. These results provide insight into the synaptic and cell type-specific mechanisms underlying alcohol addiction and identify targets for the development of new therapeutic approaches to alcohol abuse.
“Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption” by Yifeng Cheng, Cathy C.Y. Huang, Tengfei Ma, Xiaoyan Wei, Xuehua Wang, Jiayi Lu, Jun Wang in Biological Psychiatry. Published online May 27 2016 doi:10.1016/j.biopsych.2016.05.016