Research Press Release

Natural resistance to drug seeking

Nature Neuroscience

April 1, 2013

What makes some individuals more likely to become drug addicts than others - A study published in Nature Neuroscience this week finds that the strength of discrete brain circuits may contribute to the natural inclination of certain individuals to seek drugs of abuse.

Roland Bock and colleagues trained mice in a cocaine self-administration task, recording how much individual mice were likely to work to seek out a cocaine reward. They found that mice that were more inclined to seek cocaine had stronger synapses in a part of the brain called the nucleus accumbens, which is important for processing neural responses to rewarding stimuli. This brain region has two populations of cells that express different forms of the receptor for the neurotransmitter dopamine, and that have distinct patterns of projections, called the direct and indirect pathway neurons. The scientists found that the synapses of neurons comprising the indirect pathway were stronger only in those animals that failed to develop compulsive cocaine seeking behaviors. In contrast, the strengths of synapses in the direct pathway were high regardless of whether or not the mice showed a strong motivation to seek cocaine. These findings suggest that strong synapses on indirect pathway neurons may protect against compulsive drug use.

Since direct and indirect pathway neurons express distinct genes, this study could provide leads for developing new drug targets to treat drug addiction.

DOI:10.1038/nn.3369 | Original article

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