Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition

This study investigated cell-type-specific gene regulatory programs in the amygdala related to cocaine addiction. Using single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assays for transposase-accessible chromatin (snATAC-seq) in outbred rats with high and low cocaine addiction-like behaviors, researchers found that rats with high addiction index (AI) showed increased relapse-like behaviors and GABAergic transmission in the amygdala. These phenotypes were reversed by inhibiting the glyoxalase 1 enzyme. Differences in chromatin accessibility implicated transcription factors in addiction. Excitatory neurons showed greater accessibility in high AI rats, while inhibitory neurons showed greater accessibility in low AI rats.

Jessica L. Zhou, Giordano de Guglielmo, Aaron J. Ho, Marsida Kallupi, Narayan Pokhrel, Hai-Ri Li, Apurva S. Chitre, Daniel Munro, Pejman Mohammadi, Lieselot L. G. Carrette, Olivier George, Abraham A. Palmer, Graham McVicker, Francesca Telese