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One Dose of Cocaine Primes the Brain for Addiction

It isn't a myth: one dose of cocaine is all it takes to prime your brain for addiction. Scientists from the University of California at San Francisco Ernest Gallo Clinic and Research Center report in today's issue of Nature that a single exposure to the drug causes a weeklong surge in brain activity associated with forming a habit. Indeed, Antonello Bonci, Mark Ungless and their colleagues discovered that cocaine¿and very likely other drugs of abuse¿"hijack" the same chemical mechanisms that normally reinforce learning and memories in the brain.

The researchers studied long-term potentiation, a process mediated by the neurotransmitter glutamate in which the connections between neurons are strengthened during learning. But instead of focusing on LTP in the hippocampus¿as has been the norm¿they looked at the ventral tegmental area (VTA) in the brains of cocaine-treated mice. They found that glutamate activated two types of excitatory receptors on the dopamine neurons in the VTA and, as a result, these dopamine neurons showed a lasting and heightened response to glutamate.

"When you learn something, you might expect to see a change in very few synaptic connections¿the junctions between communicating neurons," Ungless says. "What's so amazing is that nearly all dopamine neurons are affected by this single cocaine exposure. This kind of response is extremely rare and would have a profound effect throughout the brain, particularly in other areas involved in addiction." The sheer extent of these brain changes means that they probably affect a range of behaviors related to drug abuse, including increased sensitivity and relapse. The challenge now, Bonci says, "is how to develop drugs that interfere with these concaine-induced changes but not with normal memory functions."

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