Drug addiction is complex and mysterious phenomenon, and it is filled with mysteries that researchers are still trying to solve. One of the greatest mysteries concerning substance abuse is understanding why some people try a drug and become addicted while others will leave the drug alone and never return to it. Equally as mysterious is why certain people are able to break the vicious cycle of addiction while others are prone to relapse.
The journey to answering these questions may lie in understanding the specific genetic marker that influences addiction, and a new study conducted by researchers at the University of Michigan may provide some preliminary answers to those questions.
The study, which was recently published in the Proceedings of the National Academy of the Sciences and featured on the University of Michigan Health System website is the first time that scientists have shown in selectively bred animals that the possibilities of developing an addiction to cocaine is linked to differences in expression of certain genes for in a specific brain region. Additionally, it is also the first study to show that a certain DNA tag called an epigenetic marker can predispose an individual to developing an addiction as well as a tendency to relapse.
Details of the Study
The subjects of this current studies were two different sets of specially-bred rats that were raised for dozens of generations under carefully controlled conditions. One breed, called bHR or bred high responders, are rats that exhibited tendencies to explore and seek out novelty. The other breed used in the study were called bLR or bred low responders and exhibited behavior that was vastly different from the bHR breed in the fact they seemed anxious when presented new stimuli and prefer sheltered spaces–even if they would see food in an open area.
These two special rats breeds allowed scientists to study the impact of drug use and addiction on both gene expression and epigenetics in the brain of known as the nucleus accumbens, which is the brain’s reward and pleasure center. In the study, researchers first trained both rat breeds to expect to find cocaine in certain places, to poke their nose into a hole to get a controlled dose of the drug , and to expect more cocaine to be available when a special light would be shone.
Although both groups of rats took the same amount of drug, the two breeds differed dramatically in how likely they were to seek out cocaine repeatedly. The study result showed that the high responding rats were much more likely to keep seeking cocaine, even if it wasn’t available. When both rat groups went a week without the drug, the bHR rats were more likely to ‘relapse’ after getting an injection of cocaine. When both rat groups went a month with no cocaine, the bHR rats were much more likely than the bLR rats to start seeking it again when the light that was previously associated with cocaine delivery started flashing.
What Were The Genetic Differences Noted By Researchers?
When studying the two rat groups, researchers discovered there were distinct differences in regards to the genetic markers that influenced addiction. First, researchers looked at the rat’s brains to find the genetic “instructions” to make a crucial pleasure receptor called D2 that allowed brain cells to receive dopamine or signals put forth by cocaine in the nucleus accumbens. The high responding rats which were more prone to addictive behavior had lower levels of D2 instructions when compared with other rats.
Additionally, the rats that were addiction prone were more likely to carry the epigenetic tag known as H3K9me3, which kept their brain cells from properly reading the gene for D2 receptors. Researchers also discovered that the more resilient rats had started out with lower levels of instructions for making a different brain molecule called FGF2 which is a brain molecule known to play a role in the development of addiction. These rats were also more likely to carry an epigenetic mark that kept them from reading the FGF2 gene, which may have protected them from becoming addicted to cocaine.
While a study on animals can’t fully explain all of the factors that contribute to differences in how addiction is expressed in human, the study does reveal new and interesting information regarding the roles played by both inherited traits and addiction-related changes in the brain.