Although much passes from father to son, a penchant for cocaine may not be part of the inheritance — as epigenetic changes confer a bit of immunity.

Investigators from the University of Pennsylvania say experiments using rats showed alterations to gene expression correlating to the brain’s nucleus accumbens — its neurons proved less sensitive to cocaine. In the animal model, repeated cocaine use by male offspring failed to evince the same brain response seen in their coke-addicted fathers. Rather, the animals appeared inured to the addictive effect of cocaine, with no remodeling of the brain to reinforce the addiction.

Normally, drug-addicted humans and other animals experience a restructuring of the brain reinforcing dependence on the drug. In brain scans, no such remodeling occurred in male offspring of the rats, though the effect was not seen in females, investigator Mathieu Wimmer reported at the annual meeting of the Society for Neuroscience in San Diego on Monday.

"This adds to the growing body of evidence that cocaine abuse in a father rat can affect how his sons may respond to the drug — and point to potential mechanisms that contribute to this phenomenon," Wimmer said in a statement. "Further research is needed to better understand how these behavior changes are passed down from one animal generation to the next, and eventually if the same holds true for humans."

The researchers believe epigenetic changes to proteins changing the expression of genetic sequences — themselves unchanging — may have conferred protection to male offspring long before they were sired, predetermining behavioral traits in future generations of rat.

Last year, Penn Medicine researchers led by R. Christopher Pierce, a psychiatric neuroscientist, found evidence that “cocaine abuse” by male rats rendered the next generation resistant to the rewarding properties of the drug — Less likely to accept cocaine offerings in the laboratory experiments, for example. Underlying these behavioral changes were alterations in the brain-derived neurotrophic factor, a molecule of central importance to the rewarding effect of cocaine.

The researchers, however, acknowledged one caveat: In the previous study, they’d only found evidence of change to neurotrophic factor in male offspring lacking exposure to cocaine. Thus, the researchers took a new approach in the new study, focusing on the physiology of neurons in male offspring — this time finding evidence, physical and behavioral, of less sensitivity to the drug.

The investigators say more research would determine whether interventions based on this action might be developed for human use.