Comparison of gene expression in the nucleus accumbens of rats expressing or not the conditioned place preference to cocaine [CPPE, nCPPE, Saline]

Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology. The objective of our study was to demonstrate and characterize the variability in the expression of the reinforcing effects of cocaine in the conditioned place preference (CPP) paradigm. An unbiased cocaine-CPP paradigm in Sprague-Dawley rats with an extinction period of 12 days and reinstatement was conducted. We developed a statistical model to distinguish rats that express or do not express cocaine-induced place preference. Two groups of rats were identified: rats that did express reinforcing effects (CPP expression (CPPE), score > 102 s) and rats that did not (no CPP expression (nCPPE), score between -85 and 59 s). These two groups did not show significant differences in a battery of behavioral tests. To identify differentially expressed genes in the CPPE and nCPPE groups, we performed a whole-transcriptome RNA-sequencing analysis in the nucleus accumbens (Nac) 24 h after the CPP test. Four immediate early genes (Fos, Egr2, Nr4a1 and Zbtb37) were differentially expressed in the Nac of CPPE rats after CPP memory retrieval. Variability in cocaine-induced place preference persisted in the CPPE and nCPPE groups after the extinction and reinstatement phases. Transcriptomic differences observed after reinstatement were distinct from those observed immediately after CPP memory retrieval. These new findings provide insights into the identification of mechanisms underlying interindividual variability in the response to cocaine's reinforcing effects. Overall design: Cocaine CPP was performed in 8-week-old Sprague-Dawley rats and the nucleus accumbens transcriptomes of CPPE, nCPPE and Saline rats were compared.