Salk Institute: Human Brain Naturally Resists Drugs

UCSD grad student Michaelanne Munoz & Associate Professor Paul Slesinger

The numbers alone are sobering:

443,000 Americans will die this year, says the Center for Disease Control, from tobacco.

In March the New York Times reported that 400,000 Americans are thought to be hooked on methamphetamine.

But the number one drug problem in America, says


Addiction costs, in both lives and in dollars. Health-related economic expense totals in the hundreds of billions of dollars annually across the country. Critics say the war on drugs was lost decades ago.

But what if the brain already comes factory-issued with an anti-addiction mechanism of its own?

Maybe it does.

According to new research by scientists at the Salk Institute for Biological Studies, a single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure.

Their findings, reported March 7 in Neuron, suggest this powerful reaction to drugs may be a protective, anti-addiction response. And, the scientists theorize that sometime in the future it might be possible to mimic this response to treat addiction to these drugs and perhaps others.

Paul Slesinger, PhD is an associate professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute in La Jolla. He explains that a healthy brain doles out rewards to itself. It is an ingenious self-congratulating mechanism such that when humans do something beneficial to the organism, the experience is rewarded and remembered. “It aids,” he says, “in survival.”

The prize comes in the form of an organic brain compound. It is a neurotransmitter called dopamine. And, every type of reward that has been studied by science is known to increase the level of dopamine transmission in the brain.

Unfortunately, so does cocaine and meth use. Add tobacco and alcohol and heroin and a host of other addictive substances.

“We know that drugs work on this part of the brain,” Slesinger says. “But what about long term changes?”

Addicts use in the face of negative consequences — no news there. Addiction produces a loss of control. No real news there, either. But over time, addict behavior becomes generated by changes in the brain’s circuitry due to abuse. “I can’t say this is a response that occurs in every person,” he says, but that is the line of reasoning that doctors at the Salk are following.

During the study the team found evidence that there is another brain circuit that actually inhibits the release of dopamine. “It could be thought of as an anti-addiction response.” In this case, mice were the test subjects. Following one injection, 24 hours to seven days later their inhibitory neurons were changed in a significant way.

“They were releasing more inhibitor on dopamine receptors,” he says, in what researchers interpreted is a possible form of a natural resistance to addictive substances.

“I think in the future what our study will allow us to do is to pinpoint the part of the nervous system that responds to certain drugs used in treatments.” Most of the compounds prescribed at present, he says, are far too general. “By focusing and targeting the changes in the inhibitory neurons we could better design a drug that affects the circuit without having wide-ranging side effects.”

The Salk team is working to identify one or two important proteins that change in response to drugs and abuse. “If we can change the protein, can we impact the behavior?” For now, that is the $64 thousand dollar question that remains to be answered for abusers, addicts, and their families. “If we could tap into this pathway and enhance the ability of inhibitory neurons to control the activity of dopamine neurons,” Slesinger says, “we might be able to treat some types of drug addiction.”

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