Scientists identify new brain mechanisms involved in impulsive cocaine search in rats

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Blocking certain acetylcholine receptors in the lateral limb (LHb), a region of the brain that balances reward and aversion, makes it difficult for researchers to resist looking for cocaine in a rat model of impulsive behavior. I found. These discoveries identify new roles for these receptors that may represent future goals in the development of treatments for cocaine use disorders. Currently, there are no approved medications to treat cocaine use disorders.

Was announced in Neuroscience journalThis study was supported by the National Institute of Substance Abuse (NIDA), which is part of the National Institute of Health. In 2020, more than 41,000 people died Overdose of drugs Contains stimulants, including cocaine And methamphetamine. Developing safe and effective medicines that help treat cocaine and other stimulant addictions is important to help expand the options offered to those seeking treatment and maintain recovery. is.

“This discovery gives researchers new concrete goals for solving long-standing elusive problems. Cocaine addiction“As we saw in drugs for treating opioid use disorders, adding this tool to clinical care can save lives from overdose and significantly improve health and quality of life.”

Researchers in addiction science are particularly interested as targets for future treatment development, as LHb occupies a position as an interface to each other. Brain region It is involved in reasoning and other higher-order thinking processes, as well as processes that mediate emotions and rewards. These are factors known to be associated with substance use disorders and major depressive disorders. For example, these areas are involved in behavioral regulation, such as withholding compensation if it is determined to be non-beneficial.

Based on previous studies that established the importance of LHb and acetylcholine receptor signaling in impulsive cocaine exploration, this study further defines the cellular mechanisms by which LHb neurons regulate this behavior. Researchers used a behavioral paradigm in rats called the Go / NoGo model. In this model, rats were trained to self-administer cocaine, and when the lever was pressed, the drug was injected. This was followed by specific training on the Go / NoGo task, where cocaine was available when the light was on (Go), but not when the light was off (NoGo). Animals have learned to stop responding immediately when cocaine is unavailable.

Next, researchers chemically engineered LHb to assess its effect on the ability of rats to refrain from responding to cocaine. They found that the inhibition of cocaine response was impaired by blocking a particular type of muscarinic acetylcholine receptor known as M.2Uses experimental drug called Rs, AFDX-116 and no drug called pirenzepine that blocks other muscarinic acetylcholine receptors known as M1Rs. Therefore, M2Rs were blocked by LHb and despite training, rodents could no longer stop responding to cocaine even when cocaine was unavailable (“No Go” state).This indicates that LHbM is increasing2The R function may represent a potential target for treating impulsive drug search and substance use disorders.

Researchers also said that M2Rs alter the activity of LHb neurons by measuring changes in the electrical activity of these neurons in response to acetylcholine-like drugs. These drugs reduced both excitatory and inhibitory inputs to LHb neurons, but there was a net increase in inhibitory. This may explain the ability of acetylcholine to limit impulsive cocaine search.

“LHb acts like an interface between rational thinking in the forebrain and regulation of neurotransmitters such as dopamine and serotonin from the midbrain. These are the decision-making process and regulation of emotions. Is important to us, “said Dr. Karl Lupica. Electrophysiology Research Section, Department of Computational and Systems Neuroscience, NIDA. “While the immediate results of this study are related to cocaine hunting, impulsivity is also associated with other drugs and mental states such as obsessive-compulsive disorder, which has a significant impact on impulsivity. Future studies. In impulsive behavior associated with LHb activity and other drugs such as cannabis, and opioids such as heroine. “

I’m targeting M2Rs are promising, and the muscarinic acetylcholine system is challenged because it is involved in everything from controlling heart rate, affecting motion sickness, and controlling vasodilation. These receptors are also present throughout the body, including many other areas of the brain. Further research is needed to develop methods for targeting M2Rs of LHb without causing a cascade of side effects, and as a first step, these researchers are now trying to identify where in the brain the acetylcholine released by LHb occurs.

Researchers have found that activating certain acetylcholine receptors in the brain reduces the use of cocaine in rodents.

For more information:
CI Wolfe et al, a muscarinic acetylcholine M2 receptor, regulates lateral rein neuronal activity and regulates cocaine-seeking behavior. Neuroscience journal (2022). DOI: 10.1523 / JNEUROSCI.0645-22.2022..… EUROSCI.0645-22.2022

Quote: Scientists obtained from on June 28, 2022 (June 28, 2022) Identify new brain mechanisms involved in impulsive cocaine exploration

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Scientists identify new brain mechanisms involved in impulsive cocaine search in rats

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