Abstract
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.
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Acknowledgements
This work was supported by College of Health Sciences – UKZN PhD Scholarship (2015–2017). The authors would like to thank South African Police Service (SAPS) for providing the cocaine powder used for this study. We also thank Prof Hans-Peter Lipp (University of Zurich, Switzerland) for IntelliCage set up and Dr. Krackow S (University of Zurich, Switzerland) for behavioural analysis of the IntelliCage data. Thanks to Prof Thavi Govender, Dr. Tricia and Dr. Yahaya (Discipline of Pharmaceutical Sciences, UKZN) for purity analysis of the cocaine powder. We also appreciate Mr. Preenan Pillay and Dr. Anand Nadar for assistance with permits and record keeping. Also, much thanks to Dr. Kogi Moodley for procurement of consumables and excellent technical assistance and Mr. Simeon Eche for help with the real-time qPCR.
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Ajonijebu, D.C., Abboussi, O., Mabandla, M.V. et al. Differential epigenetic changes in the hippocampus and prefrontal cortex of female mice that had free access to cocaine. Metab Brain Dis 33, 411–420 (2018). https://doi.org/10.1007/s11011-017-0116-z
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DOI: https://doi.org/10.1007/s11011-017-0116-z