summary: Researchers have found that the brain’s “saliency network” is activated only when drugs are taken intravenously, rather than orally, providing insight into the mechanisms of addiction.
Rapid entry of drugs into the brain, such as by injection or smoking, has been shown to be more likely to cause addiction than slower methods, such as oral ingestion.
The study used PET/fMRI imaging to compare dopamine levels and brain activity in response to methylphenidate treatment in 20 adults.
Important facts:
- A “saliency network” in the brain, associated with the perception of the subjective effects of drugs, was only activated upon intravenous administration.
- The rapid release of dopamine from intravenous administration of the drug corresponds to an increased likelihood of dependence, whereas the slow increase from oral ingestion has a lower risk of dependence.
- This study highlights the potential of targeting the saliency network to develop new treatments for substance use disorders.
sauce: NIH (National Institutes of Health)
Results of a new clinical trial suggest that a group of brain regions known as the “saliency network” is activated after taking a drug intravenously, but not when the same drug is taken orally. ing. If a drug enters the brain quickly, such as when injected or smoked, it is more addictive than if it enters the brain slowly, such as when taken orally.
However, the brain circuits underlying these differences are not well understood. This study provides new information that helps explain the cause of this difference.
This study nature communications and It will be led by researchers from the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health at the NIH Clinical Center.
“We’ve long known that the faster a drug enters the brain, the more addictive it becomes, but we didn’t know exactly why. Now, using one of the latest and most sophisticated imaging techniques This provides us with some insight,” said Nora Volkow, MD, NIDA Director, NIAAA Neuroimaging Institute Director, and senior author of the study.
“Understanding the brain mechanisms underlying addiction is critical to informing preventive interventions, developing new treatments for substance use disorders, and addressing the overdose crisis.”
People who smoke or inject drugs (two ways to quickly deliver drugs to the brain) often report doing so to get relief from withdrawal symptoms faster or to experience euphoria more quickly.
However, smoking and injecting drugs are associated with the onset of substance use disorders sooner than taking drugs orally or by inhalation (e.g., snorting). In addition, injecting drugs is also associated with increased rates of infectious disease and overdose.
To better understand how drug administration route affects the brain’s response to drugs, researchers conducted a double-blind, randomized, counterbalanced clinical trial using simultaneous PET/fMRI imaging. was carried out.
Twenty healthy adults participated in the study. Over three separate sessions, participants were given small doses of either a placebo or the stimulant methylphenidate, commonly known as Ritalin, either orally or intravenously.
Methylphenidate is a safe and effective prescription drug used to treat attention deficit hyperactivity disorder (ADHD).
For research purposes, methylphenidate can be a useful model drug to safely study the relationship between drug effects on the brain and the subjective experience of drug reward.
After participants were given the study drug or a placebo, the researchers simultaneously looked for differences in dopamine levels (via PET imaging) and brain activity (via fMRI imaging), indicating people’s subjective experience of euphoria in response to the drug. reported.
PET scans estimated how quickly dopamine increases in the brain in response to various drug administrations. Consistent with previous studies, this study showed that when participants were given methylphenidate orally, the rate of increase in dopamine peaked over an hour after administration.
By comparison, when participants received an intravenous injection of methylphenidate, the rate of increase in dopamine peaked much faster within 5 to 10 minutes after administration.
Through fMRI, the researchers observed that both oral and intravenous administration of the study drug decreased activity in one area of the brain, the ventromedial prefrontal cortex.
However, two brain regions that are part of the brain’s salience network, the dorsal anterior cingulate cortex and the insula, were activated only after receiving injections of methylphenidate, a more addictive route of drug administration.
These same areas of the brain were not activated even after oral ingestion of methylphenidate, a less likely route of addiction. This finding was consistent among all 20 study participants.
The salience network is important for attributing value to things in our environment and for perceiving and translating internal sensations, including the subjective effects of drugs.
This study adds to the body of evidence documenting the important role that saliency networks appear to play in drug use and addiction. For example, studies have shown that people who experience damage to the insular cortex, which is part of the brain’s salience network, can achieve complete remission from addiction.
In this study, the researchers also asked patients to track in real time their conscious experience of drug reward, or euphoria, in response to both oral and intravenous administration of the drug.
After administering the drug intravenously, the researchers found that the saliency network activity and connectivity observed in fMRI images closely resembled the subjective experience of feeling high in nearly all participants. I noticed that. When imaging tests showed increased activity in this part of the brain, participants reported feeling high.
When the images showed decreased activity in the salience network, participants’ reports of feeling high decreased. The researchers theorize that the networks identified in this study are related not only to drug chemistry but also to the conscious experience of drug reward.
The authors say that an important next step in this research is to study whether inhibiting the salience network effectively blocks the high feeling when someone takes the drug, and that this point out that the salience network may be further supported as a suitable target for the treatment of substance use disorders.
“I’ve been doing imaging research for over a decade now, and I’ve never seen such consistent and clear fMRI results across all participants in one of our studies. These results… , further supports the evidence that the brain’s salience network is a worthy target to study for potential new treatments for addiction,” said Peter Peters, a research scientist at NIAAA and lead author of the study. Dr. Manza said.
About this neuroscience and addiction research news
author: press office
sauce: NIH (National Institutes of Health)
contact: News Office – NIH
image: Image credited to Neuroscience News
Original research: Open access.
“Dopamine increase during drug reward is fast, but not slow, and selective neural circuits” by Nora Volkow et al. nature communications
abstract
Dopamine increase during drug reward is fast, but not slow, and selective neural circuits
The faster a drug enters the brain, the greater its addictive potential, but the brain circuitry underlying speed dependence on drug reward remains unresolved.
Dynamics of dopamine signaling in 20 adults receiving oral (resulting in slower delivery) and intravenous (resulting in faster delivery) methylphenidate administration using simultaneous PET-fMRI, brain activity/connectivity, and self-reported “high” (trial NCT03326245).
We estimated the rate of increase in striatal dopamine to oral and intravenous methylphenidate and tested where brain activity was associated with slow versus fast dopamine kinetics (primary endpoint ). We then tested whether these brain circuits were temporally associated with individuals’ “high” ratings of methylphenidate (secondary endpoint).
Corticostriatal circuits, including connections between the dorsal anterior cingulate cortex and the insula, and the dorsal caudate nucleus, were activated by a “high” rating paralleled by a rapid (but not slow) increase in dopamine.
These data provide evidence of a link between dACC/insular cortex activation and a rapid but not slow increase in dopamine in humans and document an important role of the salience network in drug reward. ing.