Inside Neuroscience: Exploring Addiction, From Origins to Treatments
Despite the increased risk of health problems, lost relationships, financial ruin, and even death, millions of people worldwide who suffer from drug and behavioral addictions cannot stop.
Researchers gathered at a press conference at Neuroscience 2013 to discuss recent studies of drug addiction, its neurobiological basis, and novel approaches to treatment. Barry Everitt of the University of Cambridge moderated the event.
Chronic Pain May Trigger Escalating Drug Use
Many factors contribute to drug abuse, and clinical studies suggest chronic pain is one of them.
Press conference presenter Lucia Hipolito of Columbia University wanted to know how pain affects drug intake in animals previously exposed to heroin. She and her colleagues trained rats to self-administer heroin before giving them a hind paw injection that caused chronic inflammatory pain. Two days later, the animals were given access to varying doses of heroin.
Compared with animals that were not in pain, the animals in pain self-administered less and worked less for the lowest heroin dose. In contrast, when exposed to the highest dose, animals in pain took more heroin than the other animals. Hipolito also found that the animals in pain required more heroin to release the same level of dopamine in the nucleus accumbens as the pain-free animals release at the lowest heroin dose.
“Our research shows that, in patients, chronic pain could trigger an escalating use of drugs, which may lead to the abuse and increased risk of drug overdose,” Hipolito said.
Lesion Studies Offer Clues About Gambling Addiction
Press conference presenters also discussed findings about behavioral addiction.
In an effort to understand whether certain brain regions are involved in gambling decisions, presenter Luke Clark and his colleagues at the University of Cambridge compared gambling behaviors of healthy people with those of people with brain injuries in the ventromedial prefrontal cortex, the insula, or the amygdala.
In one test, the researchers explored the participants’ tendency to adopt the “gambler’s fallacy” — the delusion that one spin of the roulette wheel affects the outcome of the next spin. After several spins in which the roulette wheel landed on red, healthy participants as well as those with damage to the amygdala or the ventromedial prefrontal cortex were more likely to predict the next spin would land on blue. However, this effect was abolished in people with damage to the insula, who were more likely to choose red after a longer run of red.
Another test evaluated how the participants react to “near-miss outcomes” — the fallacy that often leads people to believe a near-miss on a slot machine is a sign they are closer to hitting the jackpot. People who were healthy as well as those with amygdala damage reported increased motivation to keep playing a slot machine after matching icons almost lined up — a near-miss. People with insula damage, however, failed to show this same motivation when presented with a near-miss.
Clark suggests that these findings indicate that “in problem gamblers, who we know are susceptible to these styles of thinking, the insula region may be overactive.”
Gamblers are Slower to React to Nonmonetary Cues
Another region of interest in the study of pathological gambling is the ventral striatum, an area activated in the presence of money, food, alcohol, and sex.
Presenter Guillaume Sescousse of Radboud University in Nijmegen, Netherlands, studied whether the ventral striatum of pathological gamblers responds differently when presented with monetary vs. nonmonetary cues. He and his colleagues designed a game in which participants could either win money or see pleasant erotic pictures if they responded rapidly to a prompt while in an fMRI scanner.
Unlike healthy participants, who displayed similar reaction times to monetary and erotic cues, pathological gamblers reacted more slowly to erotic cues than to monetary cues. Imaging revealed that, during this game, the ventral striatum was similarly activated in healthy subjects regardless of whether the cue was monetary or erotic. In contrast, gamblers showed reduced activity in the ventral striatum in response to erotic cues compared with monetary cues. The more severe the participant’s gambling problem, the more pronounced the difference in the ventral striatum reactivity to monetary vs. erotic cues.
“Our study shows that pathological gambling is characterized by an imbalance in reward sensitivity,” Sescousse said. “We think this could represent a neurophysiological mechanism by which monetary cues override the incentive of nonmonetary cues and promote compulsive gambling at the expense of other rewarding activities.”
Brain Stimulation Therapies May Help Addicts Kick the Habit
Scientists hope that advances in understanding how addiction changes the brain will lead to better treatments that can help reverse those changes.
Previous studies in animals have shown that high-frequency stimulation to the subthalamic nucleus (STN) decreases animals’ motivation for cocaine. Presenter Carrie Wade of the Scripps Research Institute wanted to know whether the same was true for animals addicted to heroin. Animals that received high-frequency deep stimulation to the STN took less heroin, failed to escalate their heroin intake over time, and did not work as hard as control animals to obtain the next infusion of heroin.
“We think deep-brain stimulation has the potential to treat heroin addiction in medication-resistant patients,” Wade said.
Another stimulation therapy of interest in the treatment of addiction is deep transcranial magnetic stimulation (dTMS) — a noninvasive technique that sends electrical impulses deep into the brain to stimulate or dampen activity in large networks of neurons.
To determine how this technique might be applied to people trying to quit smoking cigarettes, presenter Abraham Zangen and his colleagues at Ben-Gurion University in Israel recruited heavy smokers who had failed at previous attempts to quit smoking. Study participants received high-frequency dTMS, low-frequency dTMS, or a sham stimulation to the lateral prefrontal cortex and insula for 13 sessions (20 minutes each) over a three-week period. Before receiving daily stimulation, half of the smokers in each group were exposed to a smoking provocation where they observed a person smoking.
After three weeks of treatment, 75 percent of participants who received the high-frequency stimulation reported cutting cigarette consumption by at least half, which was confirmed with a urine test. Of the participants who also received the provocation, 44 percent quit smoking altogether. Six months later, 35 percent of the participants who received the provocation with high-frequency stimulation treatment had quit smoking. In contrast, participants who received low-frequency or sham dTMS did not significantly decrease their smoking.
“The combination of stimulation with provocation is thought to activate the relevant networks, making it more labile for change,” Zangen explained.
Dark Side of Addiction
While scientists have long recognized the role of the reward system in addiction, presenter George Koob, director of the National Institute on Alcohol Abuse and Alcoholism and formerly of the Scripps Research Institute, described the important role the brain’s stress systems also play in addiction.
Koob discussed recent animal studies pointing to the roles of the corticotropin-releasing factor system in the amygdala and the dynorphin/k-opioid system in the basal ganglia in the negative reinforcement of addiction.
“The dark side of the neurocircutiry of addiction may involve multiple stages of the addiction cycle to initiate and perpetuate the negative emotional states that drive compulsive drug-seeking,” Koob said.