Sons of Cocaine-addicted Rats Less Likely to Want the Drug

Sons born to fathers with a history of cocaine use are more likely to show resistance to the drug and therefore less likely to develop addictive behaviors, according to a study of rats from the University of Pennsylvania School of Medicine.

Researchers found that sons, but not daughters, of male rats on cocaine were not only more likely to resist the effects of the drug, but were less likely to want cocaine at all.

The research was conducted on laboratory rats by Mathieu Wimmer, a post-doctoral researcher and R. Christopher Pierce, an associate professor of neuroscience in psychiatry at the Perelman School of Medicine at the University of Pennsylvania.

The results suggest cocaine causes alterations to DNA known as epigenetic changes in the rat's sperm in which reprogrammed information is transmitted down to the next generation of males.

In a prior study, Pierce and his colleagues found that cocaine abuse in male rats would lead to the next generation of males fathered by the cocaine-addled rat to be resistant to the rewarding properties of the drug, meaning the offspring were less likely to take cocaine. The researchers found changes in the rat's brain-derived neurotrophic factor (BDNF), a molecule known to be important for the rewarding efficacy of cocaine.

For the latest study, the researchers focused on the physiology of the rat's neurons before and after taking cocaine. Male offspring of cocaine-experienced fathers were found to be less sensitive to the drug and less likely to succumb to addictive behaviors, the researchers said.

The rat offspring of cocaine-addicted fathers, the researchers learned, were less likely to take the drug on their own volition and less likely to be come addicted to it if it is administered to them. Even if repeatedly subjected to cocaine, the sons of cocaine-experienced fathers did not undergo a remodeling of excitatory AMPA receptors, which the researchers say is considered to be critical for the development of addiction and cocaine craving.

"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," said Wimmer. "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 research is presented by the Penn Medicine researchers at Neuroscience 2013, the annual meeting of the Society for Neuroscience.