Regulation of mouse nucleus accumbens transcript levels by early life social stress and cocaine. AccumSeq

Addiction is defined as a compulsive drug use that is maintained despite adverse consequences for the user. Both genetic and environmental factors can contribute to the individual vulnerability to drug abuse and relapse to drug use. Overwhelming evidence exists for an association between childhood maltreatment (CM) and Substance Use Disorder (SUD) vulnerability and frequency of relapse to addiction. In rodents both acute and chronic stress have impact on the escalation of drug use. Early life stress (during the first two weeks of life), such as maternal separation or reduction of maternal licking and grooming, has been shown to modulate the rewarding effects of cocaine, amphetamine, and morphine in adult mice/rats. However, even if human data reveal that the exposure to an aggressive environment (e.g. physical abuse) in infancy/adolescence highly predisposes the individual to the abuse of a number of substances in adulthood, (including alcohol, cocaine, heroin, marijuana, and tobacco;), the effect of this type of experience has never been investigated in preclinical models. We have recently discovered that the exposure to an "hostile/aggressive" social environment (early social stressed, ESS) during preadolescence/juvenile age (third postnatal week) increases cocaine seeking behavior and cocaine-induced reinstatement in mice. A large-scale reconfiguration of the neuronal epigenome and an intense synaptogenesis are known to occur intensively in the mouse brain during this age.We therefore assume that experiencing an hostile social environment during this important week causes stable molecular changes in the brain that interact with variations similarly induced by the chronic cocaine in the brain’s reward circuitry. In order to further support our hypothesis, we characterized the transcriptome of nucleus accumbens (NAc), a key component of the reward circuitry, of ESS and control mice, by RNA-seq. This is a next generation sequencing technique that provides a highly precise measurement of level of transcripts (Ref). Several transcripts were observed as differentially expressed in the NAc of ESS mice. Our findings, for the first time, shed light on the molecular/biological mechanisms that maybe involved in the increased susceptibility to relapse into cocaine use of early social stressed individuals.