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Results from Rat Study May Lead to Prevention of Cocaine Addiction in Humans

By BiotechDaily International staff writers
Posted on 01 Apr 2013
Disruption of a "feed-forward loop" that links the activities of two enzymes in the nucleus accumbens region of the brain of cocaine addicts prevented or reversed addiction to the drug in a rodent model and in tissues taken from deceased human subjects.

The transcription factor delta-FosB and the brain-enriched calcium/calmodulin-dependent protein kinase II (CaMKII-alpha) were induced in the nucleus accumbens (NAc) by chronic exposure to cocaine or other psychostimulant drugs of abuse.

Investigators at Michigan State University (East Lansing, USA) reported in the March 6, 2013, issue of the Journal of Neuroscience that delta-FosB was phosphorylated by CaMKII-alpha at the protein-stabilizing serine-27 residue, and that CaMKII-alpha was required for the cocaine-mediated accumulation of delta-FosB in rat NAc. Conversely, they showed that delta-FosB was both necessary and sufficient for cocaine induction of CaMKII-alpha gene expression in vivo.

The current study further demonstrated the induction of delta-FosB and CaMKII-alpha in the NAc of human cocaine addicts, suggesting possible targets for future therapeutic intervention. These results suggest that delta-FosB and CaMKII-alpha engaged in a cell-type- and brain-region-specific positive feed-forward loop as a key mechanism for regulating the reward circuitry of the brain in response to chronic cocaine.

“Understanding what happens molecularly to this brain region during long-term exposure to drugs might give us insight into how addiction occurs,” said first author Dr. A.J. Robison, assistant professor in the physiology at Michigan State University. “The increased production of these proteins that we found in the animals exposed to drugs was exactly paralleled in a population of human cocaine addicts. That makes us believe that the further experiments and manipulations we did in the animals are directly relevant to humans.”

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