Identifying Neural Adaptations Underlying Cocaine Addiction

A new study recently published in the Proceedings of the National Academy of Sciences, demonstrated that chronic exposure to cocaine, followed by withdrawal, induces changes in the strength of connections between reward neurons in the brain.

D. James Surmeier, PhD, chair of Physiology and co-author of the paper, along with collaborators, studied the protein WAVE1, which, when activated, is associated with physical and functional decreases in the synapses of neurons that have dopamine receptors.

The authors suggest the findings demonstrate that WAVE1 is a key part of a mechanism that regulates the plasticity of these synapses in cocaine addiction.

“Addictive behavior is learned. By pinning down the molecular changes that underlie that learning, we may be able to manipulate it and blunt addictive behavior,” Surmeier said.

Using mouse models, the scientists found mice without the WAVE1 protein in neurons expressing the D1 dopamine receptor showed a decrease in place preference associated with cocaine. Furthermore, they observed in wildtype mice — but not in the WAVE1-deficient mice — a decrease in the density of dendritic spines, a protrusion from a neuron that receives input from the synapse of other neurons. They also saw a decrease in the frequency of excitatory currents in these neurons.

The study’s findings, according to the authors, help explain how cocaine use causes long-term changes in behavior by altering the synaptic strength between neurons.

This work was supported by Department of Defense US Army Medical Research Acquisition Activity Grants W81XWH-09-1-0392 and W81XWH-09-1-0402; National Institutes of Health Grants DA010044, MH090963, R01DA014133 and NS34696; and grants from the JPB Foundation.

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