Abolishing Protein in Specific Brain Cells Obstructs Nicotine Reward

The findings of a recent study have shown that by abolishing a protein from cells residing in the brain's reward center, one can obstruct the rewarding effects of nicotine.

The research was led by Tresa McGranahan, Stephen Heinemann, PhD, and T. K. Booker, PhD, of the Salk Institute for Biological Studies.

Nicotine is addictive by nature due to its ability to bind to proteins called nicotinic receptors which reside on the surface of brain cells.

The researchers discovered that eradicating a particular form of nicotinic receptor from brain cells that produce dopamine decreased the chances that their mouse models would seek out nicotine.

According to most smokers, relief from anxiety is a key factor in continued smoking or relapse. The researchers reported that the mice whose receptors had been tampered with did not exhibit reductions in anxiety-like behaviors normally seen after nicotine treatment.

"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," stated Paul Kenny, PhD, an unaffiliated expert on drug addiction at Scripps Research Institute.

Prior research has shown that blocking the alpha4 nicotinic receptor within the ventral tegmental area (VTA) reduces the rewarding properties felt through consumption of nicotine.

Due to the fact that alpha4 receptors are found on several cell types in the VTA, it was not known how nicotine fabricated feelings of gratification..

The researchers created mice with a mutation that resulted in the animals being unable to produce the alpha4 receptor but only on dopamine brain cells in order to focus on the circuit significant to the brain's response to nicotine.

The investigators found that the mice who did not have alpha4 receptors in these cells utilized less effort attempting to obtain nicotine in comparison with normal mice. This finding implies that the alpha4 receptors are necessary for the rewarding effects of nicotine.

Nicotine also did not decrease anxiety-like behaviors in the mutated mice, as it often did in the 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," said McGranahan.

The study was publishing in The Journal of Neuroscience.