Overcoming cocaine use disorder requires achieving and sustaining abstinence, the latter of which typically presents the greater challenge.

Although studies have established that drug-associated cues induce craving that strengthens during sustained abstinence, the neurobiological basis of intensified drug seeking remains unclear.

The authors examined the role of the dorsal hippocampus (DH)—a brain region tied to context-dependent cocaine seeking—in relapse vulnerability. Using a rat model, the authors found that a member of the transforming growth factor-ß superfamily, activin A, is both elevated in the DH and regulates drug seeking on day 30 but not day 1 of abstinence.

Furthermore, the authors report how activin A regulates cocaine seeking on day 30 via NMDA receptors, which mediate a reward-and-motivation signaling pathway that is remodeled by cocaine use. Synaptic strength increases through time in the DH during abstinence, and, by day 30, the DH connections to the lateral septum, a brain region implicated in vulnerability to cocaine relapse, are also strengthened.

The findings illuminate the role of the DH in cocaine seeking during abstinence, according to the authors.

https://www.pnas.org/content/early/2020/10/01/2006133117