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New paper published: Finding new ways to treat methamphetamine dependence.

TSRI Researchers Discover New Mechanism that Plays Key Role in Methamphetamine Addiction

LA JOLLA, CA – March 11, 2015 – Methamphetamine abuse and dependence is a major issue in the US. More than 1 million people used methamphetamine in the past year and its use is associated with dramatic health effects and cost the nation >20 billions dollars per year. Unfortunately, there is no FDA-approved medications to help prevent methamphetamine addiction.

Now scientists at The Scripps Research Institute (TSRI) have found that targeting a specific neurotransmitter system in the brain called Dynorphin may prevent the development of methamphetamine dependence. Their findings, published March 11 in the Journal of Neuroscience, show that blockade of dynorphin receptors in the brain prevented the escalation of methamphetamine intake in dependent rats.

“If we can develop compounds to target these receptors in humans, we might be able to prevent light users for transitioning to heavy use as well as decrease relapse rate in individuals who want to quit. ,” said Olivier George, assistant professor at TSRI.

The study lead by Dr. Tim Whitfield not only demonstrates the role of the dynorphin receptor (also known as kappa receptors) in methamphetamine intake, but also unveils the brain region where the kappa receptors are activated. Dr. Whitfield found that blockade of kappa receptors in the nucleus accumbens shell, but not core, was sufficient to reproduce the beneficial effects of the kappa antagonist on methamphetamine intake. They also found that dependent rats exhibit excessive amounts of dynorphin in the same brain region compared to non-dependent rats.

These results also validate the hypothesis that overactivation of the brain stress system is a critical step in the transition to drug dependence. Drug addiction is often viewed by the public as an exagerated, sensitized, response to reward. However, there is now converging evidence from our laboratory and other groups, that the main culprit in drug addiction is not a sensitized brain reward system, but an overactivation of the brain stress system.

The dynorphin system is a key element in the brain stress system and has a powerful control over emotions in human. For instance, activation of dynorphin receptors in human produces an aversive dysphoric-like state very similar to drug withdrawal. This theory originally developped by Dr. George Koob (on leave of absence from TSRI to direct the National Institute on Alcohol Abuse and Alcoholism) had been proven right before for alcohol and heroin dependence but not for methamphetamine. This study demonstrates that activation of the dynorphin stress system may represent a common final pathway responsible for the transition to dependence to different classes of drugs of abuse.

In addition to Whitfield, George, and Koob other authors of the study, “Kappa Opioid Receptors in the Nucleus Accumbens Shell Mediate Escalation of Methamphetamine Intake,” include Joel E. Schlosburg, Sunmee Wee, Adam Gould, Yanabel Grant, Eva R. Zamora-Martinez, Scott Edwards, Elena Crawford and Leandro F. Vendruscolo.

This study was supported by by National Institutes of Health Grant R01 DA010072 from the National Institute on Drug Abuse. Support was also provided by the Pearson Center for Alcoholism and Addiction Research at The Scripps Research Institute. Training for T.W.W. was provided by National Institute on Alcohol Abuse and Alcoholism Grant T32 AA007456 and National Institute on Drug Abuse Grant F32DA033726.

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