Differential epigenetic changes in the hippocampus and prefrontal cortex of female mice that had free access to cocaine

Duyilemi C. Ajonijebu, Oualid Abboussi, Musa V. Mabandla, William M. U. Daniels

Alterations in gene expression within the neural networks of prefrontal cortex (PFC) and hippocampus (HPC) are known to contribute to behavioural phenotypes associated with drug intake. However, the functional consequences of regulated expression patterns of Fosb and Crem (cAMP response element modulator) in both brain regions in response to volitional intake of cocaine in social environment is yet to be explored. Here, we first exposed young adult mice to cocaine (300 mg/L) and water concurrently for 30 days in the IntelliCage to investigate consumption preference, and subsequently for 28 days during which persistent motivated drug seeking behaviours were examined. Thereafter, locomotor activity and memory performance of the mice were assessed. DNA methylation status in the promoters of Fosb and Crem genes were also evaluated. We show that mice that had extended access to cocaine exhibited motivational deficit and demonstrated decreased locomotor activity and intact recognition memory. These changes were accompanied by hypomethylation or hypermethylation in the promoters of Fosb and Crem genes in the PFC and HPC of the cocaine-experienced mice, respectively. Together, these findings correlate the molecular changes to behavioural effects of the treatment and further suggests a possible activation of prefrontal cortical networks by social interaction episodes in the IntelliCage which possibly enhanced behavioural control that dampens mice sensitivity to cocaine rewards. Furthermore, our data delineate the molecular response of Crem and Fosb to oral cocaine in group-housed mice and demonstrates differential regulation of activities within the substrate brain regions studied.