Researchers ID changes that may occur in neural circuits due to cocaine addiction

A research team from the Friedman Brain Institute of the Icahn School of Medicine at Mount Sinai published evidence showing that subtle changes of inhibitory signaling in the reward pathway can change how animals respond to drugs such as cocaine. This is the first study to demonstrate the critical links between the levels of the trafficking protein, the potassium channels’ effect on neuronal activity and a mouse’s response to cocaine. Results from the study are published in the peer-reviewed journal Neuron earlier this month.

The authors investigated the role of sorting nexin 27 (SNX27), a PDZ-containing protein known to bind GIRK2c/GIRK3 channels, in regulating GIRK currents in dopamine (DA) neurons on the ventral tegmental area (VTA) in mice.

“Our results identified a pathway for regulating the excitability of the VTA DA neurons, highlighting SNX27 as a promising target for treating addiction,” said Paul A. Slesinger, PhD, Professor, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai. “Future research will focus on the role that potassium channels and trafficking proteins have in models of addiction.”


Dr. Slesinger was the lead author of the study and was joined by Michaelanne B. Munoz from the Graduate Program in Biology, University of California, San Diego and the Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California.

What is Cocaine?
Cocaine is a highly addictive stimulant that directly affects the brain. The pure chemical found in cocaine, cocaine hydrochloride, has been an abused substance for more than 100 years. Cocaine is derived from the coca plant, which grows primarily in Peru and Bolivia. People have been ingesting the leaves of the coca plant for thousands of years. In the last century, cocaine has been used by doctors to treat a variety of illnesses. Today, cocaine has some medical uses; for example, as a local anesthetic for some eye, ear and throat surgeries. However, cocaine is labeled a Schedule II drug because it is at high risk of being abused.

How is Cocaine Used?
Cocaine comes in different forms and is taken in different ways. The hydrochloride salt form of cocaine is a fine, white powder that is snorted through the nose and absorbed through the nasal tissues. Cocaine can also be dissolved in water and injected directly into the bloodstream with a needle, heightening the intensity of its effects. Other forms of cocaine include:

• Freebase cocaine, which is usually smoked, refers to a compound that has not been neutralized by an acid to make the hydrochloride salt.
• Crack cocaine is a form of freebase cocaine that comes in small lumps (“rocks”) or shavings. Crack cocaine is processed with ammonia or baking soda and water, then heated to remove the hydrochloride. “Crack” refers to the crackling sound made when crack cocaine is smoked. Like cocaine, crack cocaine is powerfully addictive and crack cocaine treatment is similar to cocaine treatment.

Researchers ID changes that may occur in neural circuits due to cocaine addiction The research was supported by grants from the National Institute on Drug Abuse, the Salk Institute Chapman Foundation, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse.


Sid Dinsay
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The Mount Sinai Hospital / Mount Sinai School of Medicine

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