Researchers have found new evidence of how cocaine withdrawal affects brain circuits. They prepared entire intact mouse brains and made them completely transparent by removing lipids then imaged them with the Wyss Center's custom built lightsheet microscope. Viral 'tags' made the neurons fluoresce. The team found that during cocaine withdrawal, neurons from the lateral Habenula - a brain area linked to depression - extend into the VTA - an area that produces dopamine, a chemical messenger that creates feelings of joy. But instead of connecting to the rewarding dopamine neurons in the VTA, they mostly connected to an anti-reward network. This reorganization of brain circuits may explain adverse behavior associated with cocaine withdrawal. The study could help clinicians understand addiction and enable people to better manage substance withdrawal.

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