To date, there are few, if any studies examining the impact of paternal cocaine use in humans, likely due to difficulties in obtaining accurate reports. Studies to date have utilized various rodent models and modes of cocaine administration to investigate potential effects of paternal cocaine on F1 offspring. Generational drug effects following maternal cocaine have been explored since the 1980вЂІs, and recent studies involving fathers provide mounting evidence that paternal cocaine exposure also influences the physiology and behavior of F1 offspring, ,, ,, ,, ]. Importantly, neurochemical and behavioral changes from drug use are not limited solely to the user. Epigenetics, defined as alterations in gene expression that do not occur through changes in DNA sequences, are thought to provide a mechanistic link contributing to the complex interactions between the environment and inherited genetics that can result in addiction. During periods of cocaine abuse, epigenetic changes create alterations to behavior and neurochemical function that can enhance addiction propensity. Collectively, these results reveal that paternal cocaine effects in F1 offspring may involve temporally limited epigenetic germline effects and identify new genetic targets for addiction research.Д¬ocaine use in the United States is an ongoing health crisis. Expression correlation analyses identified a novel target, Fam19a4, that may negatively regulate many genes in the accumbens, including genes already identified in addiction. Enrichment analyses highlight genes linked to CNS development, synaptic signaling, extracellular matrix, and immune function. RNASeq analyses of F1 accumbens tissue revealed changes in gene expression in male offspring of cocaine-exposed sires, including many genes not previously linked to cocaine addiction. Altered cocaine preference also was not observed in F2вЂІs. However, F1 offspring of sires bred 4 months after withdrawal did not exhibit altered cocaine preference. We demonstrate that paternal cocaine intake over a single Лњ40-day spermatogenic cycle significantly decreased cocaine (but not ethanol or sucrose) preference in a sex-specific manner in F1 mice from sires mated 24вЂ‰h after drug withdrawal. This study, utilizing a murine (C57BL/6J) oral cocaine model, examines the effects of paternal cocaine exposure on fundamental characteristics of offspring reward responses, including: 1) the extent of cocaine-induced effects after different durations of sire drug withdrawal 2) sex- and drug-dependent differences in F1 reward preference 3) effects on second generation (F2) cocaine preference and 4) corresponding changes in reward area (nucleus accumbens) mRNA expression. In rodents, changes in first generation (F1) offspring include drug reward behavior, circadian timing, and anxiety responses.

Paternal cocaine use causes phenotypic alterations in offspring behavior and associated neural processing.

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