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Dude, Where's My Fear?

1 August 2002 (All day)
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Forget about it. Native cannabinoids allow mice to unlearn painful associations.

The same brain receptors that make marijuana smokers forget where they left their cars are also responsible for wiping out bad memories, new research suggests. The finding could lead to treatments for posttraumatic stress and other anxiety disorders.

The cannabinoid receptor CB1 gets its name from cannabis, the first substance known to activate it. More recently, native brain chemicals were shown to activate CB1 and thereby modulate memory, appetite, and pain. But scientists have only vague descriptions of the receptor's function. Neuroscientist Beat Lutz of the Max Planck Institute of Psychiatry in Munich, Germany, and colleagues thought one of CB1's jobs might be to get rid of certain memories once they outlive their usefulness--a phenomenon called memory extinction.

To test their theory, the researchers studied normal mice and mutant mice that lack CB1. They taught both kinds of mice to develop a so-called negative association when the researchers sounded a tone and simultaneously shocked the mice. The mice learn to recognize the tone and they freeze in fear when they hear it later, even without the shock. Normal mice start to lose this fear response after about 2 days. But mice lacking CB1 often freeze even 8 days after being shocked, the team reports in the 1 August issue of Nature. Giving normal mice a drug to suppress CB1 also blocks memory extinction. By analyzing brain tissue from the genetically normal mice, the researchers showed that sounding the tone without the shock activates two cannabinoid chemicals in the amygdala, a brain region responsible for fear, suggesting that cannabinoids help the mice unlearn the link between the tone and the shock.

"This is the first time anyone has implicated CB1 in extinction," says pharmacologist Aron Lichtman of Virginia Commonwealth University in Richmond. Lutz says the findings suggest that drugs that help native cannabinoids persist longer in the brain could be a good treatment for posttraumatic stress disorder, which involves the retention of unwanted memories.

Related sites
Lutz's Web site
Lichtman's Web site

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