Dad’s cocaine use may help protect son from addiction

Cocaine use may not make you a better dad, but it may make your son a bit more resistant to addiction, says a new study conducted on rats.

Compared with the pups of rats who got no cocaine, the male offspring of rats that were allowed to self-administer cocaine for two months behaved very differently under the influence of the drug. When they got repeated doses of cocaine, rats sired by undrugged fathers responded with an escalating frenzy of movement - in rats, a sign of incipient addiction. The male offspring of fathers who went on a two-month cocaine bender did not show the same increase in motor activity - an indication they were more resistant to the drug’s rewarding effects.

The young rats’ brains told a similar story. In pups born to fathers who were cocaine virgins, the nucleus accumbens - a region that is key to reward-seeking and addictive behaviors - responded quite differently, depending on whether a pup’s father was a cocaine user. A father’s cocaine-taking history determined whether specialized neuroreceptors in the nucleus accumbens passed on an electrical current or did not, making addiction either more or less likely.

The research, presented in San Diego on Monday at the Society for Neuroscience’s annual meeting, may seem like an invitation to would-be fathers to self-medicate at will, secure in the belief their behavior will not harm their eventual offspring. But the study’s findings more likely support a very different conclusion: that even when self-destructive behavior doesn’t actually alter genetic material, one generation’s choices can profoundly - and unpredictably - influence the cerebral (and other) function of subsequent generations.

They do so, the researchers showed, not by the dramatic act of altering genes, but by altering the cascade of chemical signals that turn genes on and off - a process called epigenetics. And because different genes have diverse ways of influencing the production of proteins, and behave differently depending on where in the body they are operating, changing the “on-off” switches on them can have a panoply of unanticipated results.

It’s part of a growing science of how nurture - the circumstances in which we live and the behavior we engage in - can actually reprogram nature - the genetic blueprints that once seemed cast in stone.

In this case, the male babies of cocaine-addled fathers may be more impervious to cocaine addiction. But sometimes, when motivation or reward-seeking drives are dialed down, the result is a propensity to depression. And since the rats’ robust response to an addictive drug is a good measure of the brain’s plasticity, or ability to learn and adapt, a tepid reaction may signal other cognitive troubles ahead.

Sometimes, epigenetic processes are even subtler, not so much turning genes on and off but allowing some genes to be expressed more or less often. A study of long-term heroin users’ post-mortem brains, presented at the Society for Neuroscience meeting Sunday, showed that opiate addiction had altered the way the DNA programmed the production of proteins in the brain’s striatum - again, a part of the organ’s addiction circuitry.

Other research presented at the Society for Neuroscience - including a talk by Nobel laureate and memory pioneer Eric Kandel - demonstrated that epigenetic processes are central to the production and storage of long-term memories. That research may help explain how a previous generation’s behavior or environmental exposures might increase the rate of developmental and cognitive disorders - including autism and intellectual disabilities - in the next generation.

“DNA may shape who we are, but we also shape our own DNA,” said Schahram Akbarian of the Icahn School of Medicine at Mount Sinai in New York in introducing the studies presented to neuroscientists gathered in San Diego. “These findings show how experience or drug exposure change the way that genes are expressed, and could be incredibly important in developing treatments for addiction and for understanding processed like memory.”