Eliminating protein in specific brain cells blocks nicotine reward

July 26, 2011

Washington, DC -- Removing a protein from cells located in the brain's reward center blocks the anxiety-reducing and rewarding effects of nicotine, according to a new animal study in the July 27 issue of The Journal of Neuroscience. The findings may help researchers better understand how nicotine affects the brain.

Nicotine works by binding to proteins called nicotinic receptors on the surface of brain cells. In the new study, researchers led by Tresa McGranahan, Stephen Heinemann, PhD, and T. K. Booker, PhD, of the Salk Institute for Biological Studies, found that removing a specific type of nicotinic receptor from brain cells that produce dopamine -- a chemical released in response to reward -- makes mice less likely to seek out nicotine. The mice also did not show reductions in anxiety-like behaviors normally seen after nicotine treatment. Smokers commonly report anxiety relief as a key factor in continued smoking or relapse.

"These findings show that the rewarding and anxiety-reducing properties of nicotine, thought to play a key role in the development of tobacco addiction, are related to actions at a single set of brain cells," said Paul Kenny, PhD, an expert on drug addiction at Scripps Research Institute, who was unaffiliated with the study.

Previous studies showed blocking the alpha4 nicotinic receptor within the ventral tegmental area (VTA) -- a brain region important in motivation, emotion, and addiction -- decreases the rewarding properties of nicotine. Because alpha4 receptors are present on several cell types in the VTA, it was unclear how nicotine produced pleasurable feelings.

To zero in on the circuit important in the brain's response to nicotine, researchers developed mice with a mutation that left them unable to produce the alpha4 receptor, but only on dopamine brain cells. Mice lacking alpha4 receptors in these cells spent less time looking to obtain nicotine compared with normal mice, suggesting the alpha4 receptors are required for the rewarding effects of nicotine. Nicotine also failed to reduce anxiety-like behaviors in the mutant mice, as it normally does in healthy mice.

"Identification of the type of nicotinic receptors necessary for two key features of nicotine addiction -- reward and anxiety -- may help us better understand the pathway that leads to nicotine dependence, and potential treatment for the one billion cigarette smokers worldwide," McGranahan said. Diseases from tobacco use remain a major killer throughout the world, causing more than 5 million deaths per year.

The findings could guide researchers to a better understanding of the mechanisms of tobacco addiction and assist in the development of new drugs to treat tobacco addiction and provide relief from anxiety disorders, Kenny added.
-end-
The research was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 40,000 basic scientists and clinicians who study the brain and nervous system. McGranahan can be reached at tmcgranahan@ucsd.edu. More information on the science of addiction can be found in the Society's Brain Briefings and Research & Discoveries publications.

Society for Neuroscience

Related Nicotine Articles from Brightsurf:

Nicotine vapour more rewarding for adolescents than adults
University of Guelph researchers are the first to discover that adolescents react differently to e-cigarette vapour than adults.

Understanding the link between nicotine use and misuse of 'benzos'
Lately, misuse of prescription benzodiazepines (such as alprazolam or Xanax, and diazepam or Valium) has been linked to nicotine use.

Popular electronic cigarette may deliver nicotine more effectively than others
When it comes to nicotine delivery, not all electronic cigarettes are created equally, according to Penn State researchers.

Fetal nicotine exposure harms breathing in infants
Exposure to nicotine during development inhibits the function of neurons controlling the tongue, according to research in newborn rats recently published in eNeuro.

Diabetes drug relieves nicotine withdrawal
A drug commonly used to treat Type II diabetes abolishes the characteristic signs of nicotine withdrawal in rats and mice, according to new research published in JNeurosci.

The nicotine in e-cigarettes appears to impair mucus clearance
E-cigarette vaping with nicotine appears to hamper mucus clearance from the airways, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Truth telling about tobacco and nicotine
In 'Truth Telling about Tobacco and Nicotine,' PRC researchers explain that, although there is agreement among researchers about evidence that vaping can be less harmful than combustible cigarettes, the tobacco control community remains divided about how to communicate -- or even whether to communicate -- information about the relative risks of tobacco and nicotine products.

This is a neuron on nicotine
Newly developed sensors visually illustrate how nicotine affects cells from the inside out.

New data suggests nicotine while pregnant alters genes
A University of Houston biomedical research team is reporting that a possible cure for addiction may be found by following the pathways of significantly altered dopamine neurons in newborns who were chronically exposed to nicotine in utero.

Ex-smokers might be better off with high rather than low nicotine e-cigs
Vapers using low rather than high nicotine e-cigarettes may be using their devices more intensely, potentially increasing the risk of exposure to toxins in the vapour, according to new research funded by Cancer Research UK and published in Addiction today.

Read More: Nicotine News and Nicotine Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.