Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage.

摘要: Ethanol abuse can lead to addiction, brain damage and premature death. The cycle of alcohol addiction has been described as a composite consisting three stages: intoxication, withdrawal craving/abstinence. There is evidence for contributions both genotype sex alcoholism, but an understanding the biological underpinnings limited. Utilizing sexes genetic animal models with highly divergent severity, Withdrawal Seizure-Resistant (WSR) Seizure-Prone (WSP) mice, distinct genotype/phenotype during stages on neuroadaptation were characterized. Transcriptional profiling was performed identify expression changes consequence chronic intoxication in medial prefrontal cortex. Significant differences identified single platform tracked over behaviorally relevant time course that covered each stage addiction; i.e., after peak withdrawal, defined period abstinence. Females more sensitive ethanol higher fold differences. Bioinformatics showed strong effect data structure profiles at irrespective background. However, abstinence, observed instead between lines/phenotypes sex. Confirmation pathways inflammatory signaling following pro-inflammatory phenotype females overall suppression immune males. Combined, these results suggest influenced differentially by vs. background support development stage- sex-specific therapies maintenance sobriety.