A Most Vexing Problem

Written by Steven Barto, B.S., Psy., M.A. Theology

FOR THE FOURTH TIME this newscast I grabbed for the remote and muted yet another 90-second commercial touting the glorious new activity of gambling online. Sexy young voluptuous blondes and brunettes with plunging necklines smile seductively and splay decks of cards, gesturing. These TV ads bear the names of so-called “trustworthy” gambling institutions, and promise a risk-free day of odds-laying up to $500, failing to remind that the house always wins in the end or such games of chance would shrivel up and blow away. One TV spot says “…now you can have the name of MGM Grand Casino in your pocket.” Never has a more ironic statement been made!

Steve Rose, PhD, a certified gambling counselor and problem-gambling prevention specialist, writes, “Since the pandemic began, there has been an explosion of online gambling.” With experts warning of this ticking time bomb, responsible gambling safeguards are sparse. Admittedly, online gambling is not new. However, the pandemic accelerated demand, leading to higher rates of riskier gambling. According to a report published by the Responsible Gambling Council (RGC) of Canada, one out of three online gamblers admit to being influenced by pandemic lockdowns (1).

Due to ease of access, online platforms make it easier to use gambling as a way to cope with underlying issues such as anxiety and depression. In fact, the RGC survey found that anxiety and depression are major factors contributing to high-risk gambling. Individuals with severe depression are almost five times more likely to engage in high-risk gambling. Typical depression symptoms such as low mood, apathy, and social isolation are a barrier to people traveling to live venues to gamble. With online gambling, anxious and depressed people can engage in round-the-clock gambling while distracting themselves from their circumstances from the ease of their living room.

A Prolific Online Presence

I did an Internet search with the words the perils of impulsive online gambling. The site listed at the top of my search results was an AD, which said Pennsylvania Online Casino – Real Cash Payouts in 24 Hours! The second result listed said Best Online Casinos in PA 2021 – Get $1,500 Welcome Bonus! Internet gambling is reeling in college students and young children along with adults. The COVID-19 crisis, and the confinement and other restrictions associated with it, represent a unique situation that carries financial consequences for the population. People worrying about the future, possibly spending more time than usual online, are at risk for falling hard for distraction or “easy solutions” to their woes.

Sports gambling in particular has soared during the pandemic and continues to climb. CBS News reports that gamblers placed $4.3 billion in bets on Super Bowl LV, marking “the largest single-event legal handle in American sports betting history.” In sports betting, a “handle” refers to the total amount of money wagered by bettors. About 7.6 million people placed bets on the game through platforms like FanDuel and DraftKings, marking a 63% increase from bets place on the 2020 Super Bowl. Additionally, more than 47 million Americans placed bets on March Madness games (2). Casey Clark, a senior vice president at the gaming association, said “You weren’t going to in-person sporting events and you weren’t going to brick-and-mortar sportsbooks [where gamblers can wager on various competitions].” He said more than 100 million people live in a state where gambling is now legal. Not long ago, that was only in Nevada (3).

Salerno and Pallanti write, “The COVID-19 pandemic has exerted a dramatic impact on everyday life globally. In this context, it has been reported that the lockdown and social distancing may have exerted an impact even on gambling behavior, not only by increasing gambling behavior in those affected by this disorder but even contributing to the occurrence of new cases” (4). According to their peer-reviewed paper, studies performed in different countries around the world have reported psychological and mental health problems due to the changes caused by the pandemic, including stress, anxiety, and depressive symptoms. Moreover, the lockdown and social distancing exerted an impact on gambling behavior, not only by increasing gambling incidents in those affected, but even contributing to the occurrence of new cases of problematic gambling.

Hodgins and Stevens write, “…the impacts of the COVID-19 pandemic on gambling and problematic gambling are diverse – possibly causing a reduction in current or future problems in some, but also promoting increased problematic gambling in others” (5). The study says, “At the same time that land-based gambling accessibility decreased during the pandemic, online gambling sites continued to operate. Some media reports indicated that online gambling business flourished during this time, and that the pandemic served to promote this increasingly popular gambling format” (6). Online gambling sites typically include the full range of types of gambling, including lottery ticket sales, casino table games such a roulette, blackjack and craps, slot machines, online poker and sports betting.

Like a Drug

Gambling, a leisure pursuit for most individuals, has the potential to cause harm to the gambler, their family and the community (7, 8). It is considered to be a potentially addictive behavior, which for some individuals can lead to gambling disorder (GD). GD is found in the DSM-5 under Unspecified Other (or Unknown) Substance-Related Disorder. This category applies to presentations in which symptoms characteristic of an other (or unknown) substance-related disorder cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate, but do not meet the full criteria for, any specific substance-related disorder or any of the disorders in the substance-related disorders diagnostic class (9). It is critical to note that, according to clinical studies, gambling addiction activates the same brain pathways as drug and alcohol cravings. Online gambling is considered to be a particularly problematic gambling format given the relative lack of constraints on how and when it can be accessed, its solitary nature, and the wide variety of types of gambling available.

David Zendle says a variety of practices have recently emerged which relate to both video games and gambling. He writes, “These range from opening loot boxes, to e-sports betting, real-money video gaming, token wagering, and social casino spending” (10). A blurring of the lines has occurred between video games and gambling activities. The most widely-discussed example of this convergence are loot boxes: Items in video games that may be bought for real-world money, but which contain randomized contents. In other words, your expenditure may lead to a “goose egg,” but the risk becomes tantalizing. Loot boxes share several formal features with gambling, and there has been widespread interest in the idea that engaging with loot boxes may lead to problem gambling. The more frequently gamers use loot boxes, the more severe their gambling problems tend to be (11). Certainly, you can see how this phenomenon places chronic gamers (especially younger players) at great risk for developing a gambling addiction.

Gamblers Anonymous (GA) was founded in 1957. It is an international fellowship of people who have a compulsive gambling problem whose approach is based upon the 12-step method of recovery from addiction initially established by Alcoholics Anonymous. Related programs include Narcotics Anonymous, Cocaine Anonymous, and Over-eaters Anonymous. GA believes gambling disorder involves repeated problematic gambling behavior that causes significant problems or distress. It is also called gambling addiction or compulsive gambling. Though Gamblers Anonymous is not associated with any religious group or political affiliation, some people find the 12-step principle of surrendering your problems to a higher power to have distinctly religious overtones. However, Gamblers Anonymous is welcoming of people of all ages, religions, and racial backgrounds—you just need to want to end your gambling addiction.

Gamblers Anonymous is a community of people who want the same goal: freedom from gambling addiction. Many Gamblers Anonymous members may also be struggling with other mental health or behavioral addictions. As a group, Gamblers Anonymous members share their wisdom, experiences, ideas for maintaining recovery, and healthy habits so that others may benefit. Members offer each other support, understanding, compassion, and solace when times are tough. Often, Gamblers Anonymous members will serve as sponsors to newer members who need more intensive support or a person to call when urges hit.

Are You Addicted to Gambling?

According to the DSM-5, persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress is indicated by the individual exhibiting four (or more) of the following in a 12-month period (12):

  1. Needs to gamble with increasing amounts of money in order to achieve the desired excitement.
  2. Is restless or irritable when attempting to cut down or stop gambling.
  3. Has made repeated unsuccessful efforts to control, cut back, or stop gambling.
  4. Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble).
  5. Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed).
  6. After losing money gambling, often returns another day to get even (“chasing” one’s losses).
  7. Lies to conceal the extent of involvement with gambling.
  8. Has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling.
  9. Relies on others to provide money to relieve desperate financial situations caused by gambling

Concluding Remarks

Television advertisements for gambling sites is a huge issue with me. I am sensitive to addiction issues because of my 40-year-plus struggles with alcohol and drug addiction. Looking over the nine criteria listed above for gambling addiction, I can honestly say I exhibited much of the same obsessive behaviors as they pertained to drinking and getting high. Addiction messes with the brain chemistry of the addict by taking hostage the chemicals associated with pleasure. The “computer chips” of the brain are neurons: billions of cells that are organized into circuits and networks. Each neuron acts as a switch controlling the flow of information. If a neuron receives enough signals from other neurons that it is connected to, it fires, sending its own signal on to other neurons in the circuit. To send a message, a neuron releases a neurotransmitter into the gap (or synapse) between it and the next cell. The neurotransmitter crosses the synapse and attaches to receptors on the receiving neuron, like a key into a lock. This causes changes in the receiving cell. Other molecules called transporters recycle neurotransmitters (that is, bring them back into the neuron that released them), thereby limiting or shutting off the signal between neurons.

Drugs interfere with the way neurons send, receive, and process signals via neurotransmitters. Some drugs, such as marijuana, opioid pain medications, and heroin, can activate neurons because their chemical structure mimics that of natural neurotransmitters in the body. These chemicals are dopamine, oxytocin, serotonin, and endorphins (abbreviated DOSE). Because heroin and other substances are extremely potent compared to these naturally-occurring brain chemicals, the brain is incapable of producing them at a level that can reproduce the intensity, leading the addict to develop a craving for his or her drug of choice.

Gambling addiction works by hijacking the brain’s neurochemicals and learned behaviors that activate the brain’s reward center. Remarkably, gambling behavior in such individuals has the same capacity to stimulate the brain as does dopamine, oxytocin, serotonin, and endorphins. In addition, the gambling addict feels rewarded by the intermittent thrill of winning. When the need to win outweighs the risk of losing, the gambling addict begins to exhibit many of the criteria noted in the DSM-5 listed above. At this point, gambling is no longer a form of entertainment. Gambling, as with drug or alcohol addiction, becomes both the problem and the solution. In other words, the addict is now locked into a pattern of behavior where he or she continuously expects to replicate the early “high” of gambling or abusing addictive substances. The brain is hijacked by the randomness of reward.

Addiction can rewire the chemical circuitry of the brain to the point that it seems impossible to quit the addictive behavior. Even though gambling does not involve ingesting chemical substances, it produces the same response as any drug. Gambling addiction is not about money or greed. As the harms outweigh the entertainment value, the gambler looses control and becomes fixated on winning back losses. Because compulsive gambling is a progressive illness, the will to gamble becomes irresistible. Adolescents and teens are at risk for developing a gambling addiction at a time when social and emotional growth is most vulnerable to change. Adolescence is characterized by increased risk-taking, novelty seeking, and locomotor activity, all of which suggest a heightened appetitive drive.

Although teens can gamble casually, the pressure to “fit it” or establish “street cred,” and times of stress or depression, can trigger overwhelming urges to gamble. Widespread neurobiological changes such as shifts in brain matter composition can complicate addiction in teens. Finally, adolescents appear especially sensitive to rewarding cues, as evidenced by exaggerated neural responses when exposed to dopamine. During adolescence, brain cells continue to bloom, with notable changes in the prefrontal cortex, which is involved in decision making and cognitive control, as well as other higher cognitive functions. Accordingly, I believe additional study is indicated regarding teen risk for developing a gambling addiction.

Help is Available Right Now!
National Problem Gambling Helpline

1 (800) 522-4700
SAMSHA National Helpline
1 (800) 662-HELP

References

(1) “The Emerging Impact of Covid-19 on Gambling in Ontario,” Centre for the Advancement of Best Practices, Responsible Gambling Council (July 2020). URL: https://www.responsiblegambling.org/wp-content/uploads/RGC-COVID-and-Online-Gambling-Report_Jul.AP_-1.pdf
(2) Kristopher Brooks, “Sports Gambling Has Soared During the Pandemic and Continues to Climb,” (March 29, 2021). URL: https://www.cbsnews.com/news/sports-gambling-betting-draft-kings-fanduel-american-gaming-association/
(3) Ibid.
(4) Luana Salerno and Steffano Pallanti, “COVID-19 Related Distress in Gambling Disorder,” (Feb. 25, 2021), Frontiers in Psychiatry. URL: https://doi.org/10.3389/fpsyt.2021.620661
(5) David C. Hodgins and Rhys M.G. Stevens, “The Impact of COVID-19 on Gambling and Gambling Disorder: Emerging Data,” (April 19, 2021). URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183251/
(6) Ibid.
(7) “Spain orders ‘social shield’ to fast track gambling advertising window,” SBC News (2020). ULR: https://sbcnews.co.uk/europe/2020/04/01/spain-orders-social-shield-to-fast-track-gambling-advertising-window/
(8) “Coronavirus: Gambling firms urged to impose betting cap of 50 pound a day,” The Guardian (2020. URL: https://www.theguardian.com/sport/2020/mar/22/coronavirus-gambling-firms-urged-to-impose-betting-cap-of-50-a-day
(9) American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) (Arlington, VA: American Psychiatric Association, 2013), 585.
(10) David Zendle, “Beyond Loot Boxes: A Variety of Gambling-like Practices in Video Games are Linked to Both Problem Gambling and Disordered Gaming,” PeerJ (July 14, 2020). URL: https://peerj.com/articles/9466/
(11) In Addictive Behaviors, Vol. 96 (Sept. 2019), 26-34. URL: https://doi.org/10.1016/j.addbeh.2019.04.009
(12) American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), Ibid., 585.

The Opioid Issue: Part 1

Part One: Dangerous Prescriptions

The opioid crisis seems to hit everyone, everywhere, regardless of socioeconomic class, geography, age, profession, or religious affiliation. Overdosing on drugs, especially opiates and heroin, is now the most common cause of death for Americans under fifty years of age. I spent forty years embroiled in active addiction. It started innocently with a case of beer, but quickly led to marijuana, cocaine, and inhalants. The longer I struggled, the more hopeless I became. Friends stopped calling me or inviting me to parties. Family felt they could no longer trust me given the hundreds of broken promises and countless runs on their medicine cabinets for opiates. Although I was able to stop drinking and taking street drugs in 2008, I battled with benzodiazepines (Xanax, Ativan) and oxycodone for another eight years. I am blessed presently with nearly two years without taking narcotics.

Opiates in Pill Bottles

This epidemic has reached every corner of the United States. This is the first in a series of blog posts regarding opiate addiction in America. This series will address dangers of opiate prescriptions, collateral damage, impact on the nation’s foster care system, homelessness and addiction, troubling developments in drug rehabilitation, addiction and crime, and a Christian response to the crisis.

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Current medical opinion indicates the reason the U.S. is experiencing a disastrous epidemic of opioid abuse can be summed up in two words: pain avoidance. In the 1990s there was a proliferation of health care professionals trying to address the symptom [of pain] and not so much the underlying causes of the pain a person has. In 2015, opioid-related deaths stole the lives of over 33,000 Americans. To put this number into perspective, this outnumbers fatal car crashes and gun deaths during the same year. According to the federal government, in 2016 the nation mourned close to 64,000 deaths from drug overdoses. Two-thirds of those involved the misuse of opioids. Karl Benzio, M.D., a Christian psychiatrist and member of Focus on the Family’s Physicians Resource Council (PRC), fears the toll could reach 80,000 deaths in 2018.

We wouldn’t be here if opioids weren’t so effective. Americans want something for their pain—regardless of whether that pain is physical, mental, or emotional. We live in a psychologically compromised society that is impatient and entitled, whose citizens feel there should be no pain in life. Accordingly, greater demands have been made on providers to eliminate all pain with medication. The problem is—and I know this all too well firsthand—once a patient gets a taste of the relief, some develop a dependence that leads them down a dark path. Ironically, that path leads only to deeper struggles. For some, the exit will only come in the form of fatal overdoses as opioids shut down the body’s ability to breath.

It is time we start helping patients deal with life’s pain and its root causes head-on, rather than masking it through medication.

How it All Began

Chronic Pain The Silent Condition

The current crisis can be traced back nearly forty years. Medical researcher Hershel Jick and graduate student Jane Porter of Boston University Medical Center analyzed data from patients who had been hospitalized there. Close to 12,000 had received at least one dose of a narcotic pain medication during their stay. Of those, Jick and Porter’s analysis found only four had developed a well-documented addiction. Jick sent the findings to the New England Journal of Medicine, who published his analysis as a letter to the editor in 1980. “Despite widespread use of narcotics [sic] drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction,” Jick wrote. Unfortunately, this quote was given far more merit than it deserved. Moreover, the conclusion had not been subjected to peer review.

In 1990, Scientific American called the Jick/Porter research “an extensive study.” About a decade later, Time proclaimed it “a landmark study.” Most significantly, Purdue Pharmaceuticals, maker of the popular narcotic OxyContin, began a promotion asserting less than one percent of patients treated with their time-released opiate medication OxyContin would become addicted. In the 1990s, pain was correlated with a greater probability of a patient having ongoing health issues. So the medical community elevated it to the position of the fifth vital sign along with heart rate, blood pressure, body temperature, and respiratory rate. The medical community, thinking that reducing pain would help long-term patient satisfaction, health and outcomes, started to prescribe more pain meds.

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The ’90s also saw the development of stronger and more effective opioid painkillers. As the decade drew to a close, the opioid epidemic was ignited. It took some time for most of the country to realize the metaphorical fuse had been lit, but the numbers back up this concern. According to the U.S. Department of Health and Human Services (HHS), between 2000 and 2017 opioid prescriptions increased 400 percent. Between 2000 and 2010, misuse involving noncompliance with prescription instructions or using medications prescribed for another person doubled. Now, the results are playing out in heartbreaking fashion nationwide, which are impossible to ignore. Overdose deaths—116 per day, according to federal statistics—are shaking Americans of all incomes, ages, and ethnicity. From the rural back roads of Appalachia (Kentucky, West Virginia) to the urban sprawl of New York and Los Angeles, the epidemic is cutting a path that threatens to leave no family unscathed.

The Blame Game

It’s become quite popular (if not convenient) to lay the blame for the epidemic squarely at the feet of the big pharmaceutical companies. For example, according to an article in the Los Angeles Times in May of this year, more than 350 cities, counties, and states had filed lawsuits against makers and distributors of opioid painkillers. The LA civil action accuses drugmakers and distributors of deceptive marketing aimed at boosting sales, claiming the companies borrowed from the “tobacco industry playbook.” One of the companies most frequently put under scrutiny has been Purdue Pharma, maker of OxyContin.

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In May The New York Times called Purdue “the company that planted the seeds of the opioid epidemic through its aggressive marketing of OxyContin.” The Times article uncovered a disturbing report on OxyContin compiled by the U.S. Department of Justice, which found that Purdue Pharma knew about and concealed significant incidents of abuse of OxyContin in the first years after the drug hit the market in 1996. The article further noted that Purdue Pharma admitted in open court in 2007 that it misrepresented the data regarding OxyContin’s potential for abuse.

Overdose Deaths Not Just Related to Opiate Prescriptions

Government reports have recently stated that today’s increase of fatal opioid-related overdoses is being driven by abuse of heroin and illicit fentanyl. A study prepared by the National Institute on Drug Abuse last September found that overdose deaths from heroin and other drugs laced with fentanyl increased 600 percent between 2002 and 2015. Street dealers have increasingly been cutting their drugs with fentanyl—a particularly dangerous and relatively inexpensive substance 50 to 100 times more powerful than morphine—to boost their profit margins. In most cases, the users don’t even realize they’re buying fentanyl-laced products.

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It is important to note that although many people believe Big Pharma is complicit in fueling the epidemic and should shoulder the loin’s share of the blame, Dr. Benzio sees it differently. “Pharmaceutical companies only make the meds,” Benzio says. “Only about 6 to 8 percent of people who take an opioid will misuse or overuse it in a destructive way. It is the doctors who over-prescribe and a society that is looking for a quick fix and can’t tolerate any discomfort [that’s to blame].”

The Road Ahead

The opiate epidemic may have grown somewhat quietly, but the nation’s attention is riveted to it now and policymakers aren’t sitting still. In 2016, Massachusetts became the first state to limit the duration for painkiller prescriptions at seven days. Since then, more than two dozen other states have also established limits. In my home state of Pennsylvania, Governor Tom Wolf initiated a statewide prescription drug monitoring system to help prevent prescription drug abuse. Of concern is the practice of “doctor shopping,” which involves a patient visiting multiple doctors and emergency departments in search of opioids. Unfortunately, this is something I did quite often while in active addiction. This practice often necessitates filling prescriptions at multiple pharmacies. The governor’s new policy includes the monitoring program, a standing order for naloxone (Narcan, used to reverse the effects of an opiate overdose), a patient non-opioid directive (which allows patients to opt out of opioid pain medicine in advance) a “warm hand-off” where ER attending physicians and other providers can set up a face-to-face introduction between a patient and a substance abuse specialist, and revised prescribing guidelines relative to opiates.

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At the federal level, President Donald Trump declared the opioid crisis a public health emergency in 2017, and formed a commission to fight it. Meanwhile, HHS now has a multi-pronged strategy to get the crisis under control, including getting better data through research and improving prevention, treatment, pain management, and recovery services. The federal crackdown is estimated to cost $13 billion to $18 billion over the next two years. Dr. Benzio believes this is “a good start,” but said providers must resist the urge to automatically jump to the quick fix of narcotics for those in pain. “There are many ways to combat pain through physical therapy and fitness, relaxation, better sleep and nutrition,” says Benzio. It seems likely that we will not get a significant handle on opioid abuse until the core issues that lead people to the drugs are addressed.

The Christian Perspective

W. David Hager, M.D., a member of the PRC, notes three principle root issues in addiction: rejection, abandonment and abuse. Hager has been a facilitator for the Christian program Celebrate Recovery. He said, “Unless we enable [people] to identify their root issue and deal with it first, the rates of relapse are high. When they are able to deal with their root issues by offering forgiveness, making amends, and seeking a personal relationship with Jesus Christ, we find that large numbers are able to enter and maintain sobriety.” That is why the Church has the unique ability to make a difference in combating the opioid crisis.

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“We have to convince faith-based communities to get their hands dirty, to get involved and realize that this is an issue,” Benzio says. He suggests inviting laypeople to develop a working knowledge of dopamine, the brain chemical that provides the pleasure-inducing sensation many who use drugs are seeking. “There is only one [higher] power that can sever synapses in the brain that have been stimulated by a substance to achieve [a certain] dopamine level,” he adds, “and that’s the power of the Holy Spirit.”

Exactly how Christians appropriate the Spirit’s power to take on the opioid crisis will vary from case to case. The point, Benzio and Hager say, is that this needs to become a top-of-mind concern for the Church. But are North American churches up to the mission of addressing opioid use among their members? Pastors are in a unique position to proclaim and demonstrate the Gospel to individuals struggling with addiction. Many are too ashamed to confess an addiction to pain medication. As the opioid crisis deepens, so must the response of the local church. If the Christian church has anything to offer those hurting from drug addiction, it is hope and community. I was only able to break the bondage of addiction over my life through the Power in the Name of Jesus.

Power in the Name of Jesus

Programs such as Narcotics Anonymous and Celebrate Recovery have been extremely effective in changing lives, but it’s not always enough. Addressing the root of addiction is one of the most effective long-term solutions, which for Christians is about the heart. The church must be willing and capable of seeing those struggling with addiction as not merely a program of the church’s community outreach; these individuals are children of a God who loves them no matter their current condition. I believe America’s recovery can find its roots in the local church.

What does love look like? It has the hands to help others. It has the feet to hasten to the poor and needy. It has eyes to see misery and want. It has the ears to hear the sighs and sorrows of men. That’s what love looks like. -St. Augustine

 

 

Why Do Addicts Take a Drug That No Longer Gives Pleasure?

People who have used cocaine for a long time report a paradoxical-seeming experience: The pleasure they get from taking the drug decreases even as the drug intensifies its hold over their behavior.

A recent NIDA-supported study sheds light on why this might be. Researchers shows that, in mice, a cocaine-induced imbalance in the activity of two key populations of neurons in the reward system persists for a longer period after repeated exposure to the drug. For long-term users, the researchers suggest, this change could both weaken the cocaine “high” and strengthen the compulsion to seek the drug.

A Distorted Ratio

Drs. Congwu Du and Yingtian Pan and colleagues at Stony Brook University in New York and at NIDA injected two groups of mice with a single dose of cocaine (8 milligrams per kilogram of body weight). One group of mice had already been exposed to the drug daily for 2 weeks, and the other, a control group, was receiving the drug for the first time. Using a novel dual-imaging and measurement technique*, the researchers tracked the drug’s impact on activity levels of two populations of medium spiny neurons (MSNs) in the striatum of the two groups of mice.

One of two MSN populations observed by the researchers interacts with dopamine via receptors called D1R. When activated by dopamine, striatal D1R MSNs give rise to pleasurable feelings, motivate an animal or a person to repeat the experience that yielded these feelings, and promote the conversion of such motivation into action by stimulation neurons in the brain’s motor cortex. The other MSN population interacts with dopamine via a different receptor, called D2R. When activated, D2R MSNs counter the effects of the D1R MSNs. They attenuate euphoria and drug seeking and inhibit the motor cortex.

In the experiment, Drs. Du and Pan found that immediately after the cocaine injection, D1R MSN activation increased and D2R MSN activated decreased, both in the mice that had been exposed daily to the drug and in those being exposed for the first time. As a result, in both groups, the ratio of D1R MSN to D2R MSN activation shifted sharply in favor of the D1R MSNs and their reward- and motivation-promoting effects.

At 5 to 7 minutes post-injection, however, the D1R to D2R activity ratios diverged between the two groups of mice. In the control mice, D1R activation rapidly fell back to its baseline level, causing the D1R to D2R ratio to also return to near baseline. In the mice that had been exposed daily to cocaine, in contrast, the cocaine-induced D1R activation increased steadily over the entire 30 minutes that the animals were observed. As a result, D1R to D2R rose higher and remained elevated longer in the daily-exposed mice holds in people as well, it could help explain why long-term users of cocaine report less euphoria from taking the drug.

The researchers propose that the drawn-out time course of cocaine-induced D1R to D2R MSN activation following repeated exposure will also enhance an animal’s or a person’s drive to seek the drug. Dr. Pan explains, “Dopamine both activates and inhibits brain circuits, and normally this dual action produces healthy behavioral outcomes. Cocaine upsets this balance. It enhances the D1R MSN signaling that normally puts a brake on those behaviors. In our experiment, we showed that this imbalance is short lived in mice when they are exposed to the drug for the first time, but long lasting in mice that have already been repeatedly exposed.”

More Research is Needed

“The research field had not put much effort into separating how these two dopamine receptor systems are involved in rewiring the brain exposed to chronic cocaine use, or their effects on compulsive intake of the drug,” says Dr. Nora D. Volkow, NIDA Director and a collaborator on the study. “This work highlights the importance of the relative participation of D1R versus D2R signaling.”

Drs. Du and Pan have more work to do to show that their observations account for long-term cocaine users’ reduced enjoyment and increased compulsion to use the drug. As a first step, they plan to examine whether increasing the D1R to D2R MSN activity ratio indeed increases animals’ drug-seeking behavior. This will be very challenging, says Dr. Du, because it will require adapting their imaging technique to monitor MSNs in awake and moving animals. To date, they have used it only with anesthetized and restrained animals.

Another outstanding question is whether long-term cocaine use actually changes the time course of D1R MSN activation in people as it does in mice. Dr. Pan notes that although research has not yet addressed this question, imaging studies conducted in Dr. Volkow’s laboratory have shown that cocaine dampens D2R signaling in people as well as mice. If further investigations confirm the researchers’ hypotheses, says Dr. Volkow, “treatments that strengthen D2R signaling could help people stop using cocaine.”

Source

Park, K.; Volkow, N.D.; Pain, Y.; Du, C. Chronic cocaine use dampens dopamine signaling during cocaine intoxication and unbalances D1 over D2 receptor signaling. The Journal of Neuroscience, 33(40):15827-15836, 2013.

*To achieve their observations, Drs. Du and Pan developed a dual-imaging technique based on a novel microprobe that was used for visualizing individual neurons deep within the brain. The technique enabled them to distinguish the populations of D1R and D2R MSNs, and to track moment-to-moment changes in each one’s calcium levels. Calcium levels directly reflect a neuron’s level of activation.