Depression-like behaviors in mice following cocaine withdrawal can be reduced by disrupting neuronal communication in a specific brain region, reports a study published online this week in Nature Neuroscience.

Withdrawal from addictive substances such as cocaine can produce anxiety- and depressive-like states that further contribute to drug abuse. In order to better understand the neural underpinnings of such phenomena, Manuel Mameli and colleagues examined neurophysiological responses in mice following cocaine exposure. The scientists found an enhancement of communication from the lateral habenula, a brain region known to respond to unpleasant events, to another region called the rostromedial tegmental nucleus, in cocaine-exposed mice. This enhancement is long-lasting, persisting for several days after initial drug exposure. The study also shows that a small protein that can disrupt the enhancement of neuronal communication can mitigate depression-like behaviors induced by cocaine withdrawal in mice.

While the potential application for clinical intervention will require further studies, this research identifies candidate molecular and anatomical targets for potentially reducing drug-associated negative emotional states such as depression. It also demonstrates that drug-evoked negative symptoms may be attributed to a specific region of the brain that processes other unpleasant events.