New research shows that the “salience network” in the brain is triggered by intravenous drug administration but not by oral consumption, providing insights into why certain approaches of drug administration are more addictive and highlighting potential targets for addiction treatment.
NIH research study suggests the brains “salience network” is important for understanding substance usage condition, could be a future restorative target.
Outcomes from a brand-new scientific trial recommend that a group of brain areas known as the “salience network” is activated after a drug is taken intravenously, however not when that exact same drug is taken orally. When drugs get in the brain rapidly, such as through injection or smoking, they are more addictive than when they go into the brain more gradually, such as when they are taken orally.
Research Background and Motivation
The study was published in Nature Communications and led by researchers at the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the National Institutes of Health, at the NIH Clinical Center.
” Weve known for a long period of time that the much faster a drug enters the brain, the more addictive it is– however we havent understood precisely why. Now, using among the most recent and most advanced imaging innovations, we have some insight,” stated Nora Volkow, MD, NIDA Director, chief of the NIAAA Laboratory of Neuroimaging, and senior author on the study. “Understanding the brain systems that underlie addiction is essential for informing prevention interventions, establishing brand-new treatments for compound use conditions, and attending to the overdose crisis.”
Study Design and Methodology
People who smoke or inject drugs– two approaches that provide drugs to the brain rapidly– often report doing so to get faster remedy for withdrawal or to experience ecstasy more quickly. Drug smoking and injection are associated with establishing a substance usage disorder more rapidly than taking drugs orally or by insufflation (e.g., snorting). In addition, injecting drugs is also connected with higher rates of infectious illness and overdose. To better comprehend how path of drug administration impacts the brains action to the drug, researchers performed a double-blind, randomized, reversed clinical trial utilizing simultaneous PET/fMRI imaging.
Twenty healthy adults took part in the trial. Over three separate sessions, individuals got either a little dose of a placebo or of the stimulant drug methylphenidate, commonly understood as Ritalin, orally or intravenously. Methylphenidate is a safe and effective prescription medication utilized for the treatment of attention deficit hyperactivity disorder (ADHD). For research functions, methylphenidate can be a helpful model drug to securely study the relationship in between how drugs affect the brain and the subjective experience of drug reward.
Results: Dopamine Levels and Brain Activity
After participants got the study drug or placebo, scientists then simultaneously took a look at differences in dopamine levels (through PET imaging) and brain activity (through fMRI imaging) while people reported their subjective experience of ecstasy in reaction to the drug.
The PET scan offered a quote of how fast dopamine increased in the brain in action to the various drug administrations. Consistent with previous research study, this study showed that when individuals got methylphenidate orally, the rate of dopamine increases peaked more than an hour after administration. Relatively, when participants received an intravenous injection of methylphenidate, the rate of dopamine increases peaked much faster– within 5 to 10 minutes of the administration.
Through the fMRI, scientists observed that one brain region, the ventromedial prefrontal cortex, was less active after both intravenous and oral administration of the study drug. Two brain areas, the dorsal anterior cingulate cortex and the insula, which are part of the brains salience network, were triggered only after receiving the injection of methylphenidate, the more addicting route of drug administration.
The salience network associates value to things in our environment and is necessary for recognizing and translating internal experiences– consisting of the subjective effects of drugs. This research study contributes to a growing body of proof documenting the crucial role that the salience network appears to play in substance usage and addiction. For circumstances, studies have shown that individuals who experience damage to the insula, part of the brains salience network, can have a complete remission of their dependency.
Implications and Future Research
After receiving the drug intravenously, researchers noticed that the activity and connectivity of the salience network, observed by means of fMRI imaging, really carefully paralleled nearly every individuals subjective experience of feeling high. Scientists theorize that the network recognized in this research study is relevant not simply for the chemical action of the drug, but also the conscious experience of drug reward.
The authors note that an essential next action for this research study will be to study whether inhibiting the salience network when somebody takes a drug effectively obstructs the sensation of being high, which could further support the salience network as an appropriate target to treat substance usage conditions.
” Ive been doing imaging research for over a decade now, and I have never ever seen such consistent and clear fMRI results across all participants in among our research studies. These outcomes include to the proof that the brains salience network is a target deserving of examination for prospective brand-new treatments for dependency,” said Peter Manza, PhD, research study fellow at NIAAA and lead author on the study.
Recommendation: “Neural circuit selective for quick but not slow dopamine increases in drug reward” by Peter Manza, Dardo Tomasi, Ehsan Shokri-Kojori, Rui Zhang, Danielle Kroll, Dana Feldman, Katherine McPherson, Catherine Biesecker, Evan Dennis, Allison Johnson, Kai Yuan, Wen-Tung Wang, Michele-Vera Yonga, Gene-Jack Wang and Nora D. Volkow, 8 November 2023, Nature Communications.DOI: 10.1038/ s41467-023-41972-6.
Results from a new scientific trial recommend that a group of brain areas known as the “salience network” is triggered after a drug is taken intravenously, but not when that same drug is taken orally. Individuals who smoke or inject drugs– two methods that deliver drugs to the brain quickly– typically report doing so to get faster relief from withdrawal or to experience euphoria more rapidly. To better understand how route of drug administration impacts the brains response to the drug, researchers performed a double-blind, randomized, reversed clinical trial utilizing synchronised PET/fMRI imaging.
For research functions, methylphenidate can be a beneficial model drug to safely study the relationship between how drugs affect the brain and the subjective experience of drug benefit.
Researchers theorize that the network identified in this study is pertinent not just for the chemical action of the drug, however likewise the conscious experience of drug reward.