Transgenerational Epigenetic Effects of Cocaine on Circadian Behavior and Cocaine Reward

Victoria Shaker, Ashley Shemery, Alex Yaw, & J. David Glass.

Department of Biological Sciences and School of Biomedical Sciences

Professor Glass served as the primary advisor. Ashley Shemery and Alex Yaw served as co-advisors.

Hypothesis: Cocaine irreversibly lengthens circadian period (tau), which could underlie the significant health issues of cocaine addiction. Others have reported that rewarding effects of paternal cocaine use are transgenerational. We hypothesize that the disruptive effects of cocaine on tau may also be transgenerational, causing altered subjective cocaine reward response in offspring (F1).

Methods: Male mice were exposed to cocaine-water (0.5 mg/ml) or water (control) for 6 wks. Immediately following treatment, the mice were mated with cocaine naïve dams. F1 reference for cocaine or sucrose (to test for reward specificity) was analyzed using a dual bottle (water and drug [0.15 mg/ml] or sucrose [2%]) free-choice regimen. Tau was analyzed using activity sensors with computerized data acquisition.

Results and Conclusions: Lengthened tau was evident in sires with forced cocaine compared to controls (24.18+0.17 vs. 24.07+0.02; p0.05). These data reveal that there is no transgenerational transmission of cocaine-lengthened tau in F1 males, but there was an alteration of tau in F1 females. Significantly, paternal cocaine intake significantly altered F1 preference for cocaine, but not sucrose, suggesting specificity to drug reward. Thus, cocaine addiction could involve a transgenerational paternal mode of inheritance.

Keywords: epigenetics, transgenerational, cocaine, sucrose, mice, sex differences, drug abuse, circadian, biological rhythms, addiction