Genetic differences in estrous cycle effects on the rat brain transcriptome

Males and females often differ on propensity for a substance use disorder (SUD), etiology and clinical manifestation of SUD, and response to SUD treatment strategies (Riley et al 2018). The fluctuation of sex-related hormones in the brain and/or circulation may contribute to some of these differences. For example, estradiol activity has been associated with sensitivity to drugs of abuse (Tonn Eisinger et al 2018) and vulnerability to SUD (Anker and Carroll 2011). In particular, estrogen can affect the dopamine system in brain and this may contribute to differences in the etiology and the clinical manifestation of SUD (Bobzean et al 2014). Without direct association with SUD, others have shown that stage of the estrous cycle influences RNA transcription levels and splicing in particular brain regions (Duclot and Kabbaj 2015; DiCarlo et al 2017). What has not been thoroughly explored is whether genetic factors can modify the effect of estrous cycle on RNA transcript and ultimately, whether the interaction of these two factors can influence the sex-related differences in SUD vulnerability. Overall design: Examination of the interaction between sex/estrus cycle and genotype using two inbred rat strains (BN-Lx and SHR), female rats across 3 different stages of the estrus cycle and male rats on brain RNA expression.