Artificial Reactivation of a Cocaine-Associated Ensembles in the Dorsal Dentate Gyrus Attenuates Cocaine Prime-Induced Reinstatement of Drug-Seeking

Optical reactivation of dorsal dentate gyrus ensembles tagged to the first cocaine exposure attenuates cocaine prime–induced reinstatement of cocaine conditioned place preference in C57BL/6 mice, but fourth-exposure reactivation does not.

• Why it matters: Relapse after abstinence is often triggered by drug primes and cues, and persistent hippocampal contextual memories may shape whether drug-seeking returns.
• What they did: Male and female C57BL/6 mice were tagged with TetTag in dorsal dentate gyrus for ensembles encoding first or fourth cocaine exposure (15 mg/kg, i.p), then underwent CPP, extinction, and reinstatement with optical reactivation versus saline-ensemble controls.
• The result: Reactivating first-exposure cocaine engrams alone did not reinstate CPP, yet it reduced cocaine-induced reinstatement, while fourth-exposure engram reactivation lacked this protection; saline-ensemble reactivation reduced cocaine-induced reinstatement in females.

AI summary of the abstract · may contain errors · not medical advice · read the paper.