Increasing research has identified a primary circadian clock gene linked to drug addiction. According to scientists, the same gene that governs the body’s many circadian rhythms also plays a key part in regulating the brain’s reward system and could potentially influence the likelihood of addictive behavior.

How Circadian Rhythms Impact Addiction

Addiction has long been a mostly silent epidemic despite its wide-reaching social and economic consequences. Just within the United States, over 63 thousand people die each year from drug overdoses. According to data from the CDC, on average, 115 Americans will die every day from opioid overdoses alone. For some scientists, it has become a moral imperative to better understand the mechanisms underlying addictive behaviors.

Research has found that substance abuse disorders often coexist with circadian rhythm disruptions, including interference with sleep-wake cycles. These disruptions further aggravate the symptoms of addiction. In addition to environmental factors, molecular disturbances of circadian mechanisms may actually predispose some people to addictive behavior. Researchers have begun devoting their efforts to better unpacking what seems like a two-way relationship between addiction and our biological clock.

In a report published online by the Proceedings of the National Academy of Sciences, researchers examined how the gene that maintains the body’s circadian clocks may also be a key player in drug addiction. The researchers found that the body’s master clock gene helps to regulate the brain’s reward system. Acting as a negative regulator for drug rewards, the gene potentially influences the addictive qualities of drugs like alcohol, cocaine, methamphetamines and opioids.

According to the lead author of the study, Dr. Colleen A. McClung, “we found that the Clock gene is not only involved in regulating sleep-wake cycles, but is also very involved in regulating the rewarding responses to drugs of abuse. It does so through its actions on dopamine pathways.”

Dopamine, Negative Rewards and Addictive Behaviors

Often abused drugs such as alcohol and cocaine rely directly on the dopaminergic reward system and other signaling pathways to promote their addictive properties. Within the brain, dopamine acts as a neurotransmitter that controls the reward and pleasure centers. Dopamine is responsible for regulating movement and emotional responses. It is what enables us to be aware of rewards, what spurs us into action to seek out those rewards, and what inevitably provides the rewarding feelings of enjoyment from stimuli.

Other studies have highlighted the role of circadian rhythm in the regulation of dopaminergic reward activity. Nearly all aspects of the dopamine reward system are subject to circadian influence and show patterns of diurnal variation.

Within their work, McClung’s team observed that when mice lacking the Clock gene were given cocaine, they were impacted more by the drug when compared to mice possessing the Clock gene. The clock-deficient mice were more hyperactive, experienced greater circadian disruption and were rewarded with a higher production of dopamine than the control mice.

According to Dr. McClung,”we tracked dopamine cells in the mice brains and found that these cells fired more rapidly and showed a pattern called bursting, which leads to an unusually large dopamine release. We also found that more dopamine is produced and released in these mice under normal conditions and particularly after exposure to cocaine.”

The team believes this suggests that the Clock gene controlling the body’s circadian rhythms is also a key regulator in the brain’s reward system. If so, it may bear a direct influence on the addictive qualities of drugs like cocaine.

Further Research on Clock Gene Linked to Drug Addiction

Eric Nestler, M.D., Ph.D., the senior author of the study thinks their results suggest that a link may exist between circadian rhythm disruption and the likelihood of abusing drugs. According to Dr. Nestler, “most work on Clock has focused on the brain’s master pacemaker, located in a brain area called the suprachiasmatic nucleus. The novelty of Dr. McClung’s findings is the role Clock plays in brain reward pathways. The next step is to examine Clock and related genes in human addicts.”

As it turns out, there may be quite a few circadian genes associated with addictive behaviors. In one study published in Behavioural Brain Research, researchers from Dartmouth investigated how the Period family of genes, related to the sleep-wake cycle, were associated with alcohol abuse. The researchers found that mice with a mutated Per gene were more likely to binge drink, having a higher tolerance for alcohol and metabolizing it at a lower rate than mice without the mutation.

In another study published in the journal Genes, Brain, and Behavior, a particular circadian rhythm gene, CSNK1E, has been directly associated with binge eating, opioid addiction, and may also play a role in some alcohol addiction cases. The authors of that study, researchers from the Boston University Medical Center, were quoted as saying, “the potential interaction of CSNK1E with circadian biology in affecting addiction is an unexplored area of investigation that could be a crucial piece to the puzzle in fully understanding its role in the addictions.”

Further research is needed to fully understand the mechanisms underlying the relationship between circadian rhythms and addiction, but it is clear that a two-way link does exist, and this knowledge may help pave the way for better understanding and treating addiction in the future.