As to date, human genetic studies have shown that cocaine addiction is heritable. Shocking? Not really. When you think of a cocaine addict producing offspring, you’d assume that the offspring would be at high risk or rather, predisposed to using cocaine. We’ve thought for years that yes, addiction is heritable and tends to run in families. But what if it’s not? What if there was some type of protective effect that could be passed down to offspring from a paternal or maternal cocaine abuse? A study published in 2013 titled, Epigenetic Inheritance of a Cocaine Resistance Phenotype, suggested just that.
The goal of this study was to examine the influence of paternal cocaine self- administration of cocaine reinforcement in offspring. What they did was allow male rats to self -administer cocaine for 60 days while the control group self -administered saline. All male rats were then mated with healthy female rats. The graph below shows the extent to which male and female offspring self administered cocaine when given the opportunity to take both low (0.5mg) and high ( 1.0mg) doses. What they found was not at all what they hypothesized. The male offspring of “cocsired” rats (fathers who self-administered cocaine) when given the opportunity to self-administer cocaine, self-administered a significant less amount of cocaine, regardless of dosage offered, than male offspring of “salsired” (fathers who self-administered saline) rats. There was no difference between female offspring in regards to self-administration of cocaine, regardless of whether their fathers were cocsired or salsired. Meaning that, female offspring whose fathers self-administered cocaine self-administered the same amount of cocaine as female offspring whose fathers self-administered saline.
Brain derived neurotropic factor (BDNF) in the medial pre-frontal cortex is known to blunt the behavioral effects of cocaine. So essentially, with a larger expression BDNF one would be less likely to experience the rewarding effects of cocaine. So, in order to ensure that it was an increase in BDNF protein causing reduced administration of cocaine in cocsire rats, they administered a TrkB antagonist called ANA-12. The reason being is that BDNF signals primarily through TrkB receptors. So because the antagonist would inhibit BDNF from binding, we should see a reverse or increase in administration of cocaine, and this is what they found. What does this mean? BDNF expression in the medial pre-frontal cortex reduced cocaine administration in cocsired male offspring.
Shocking? Yeah, I’d say so! This study suggests that exposure to cocaine in father rats might cause some kind of protective effect in their male offspring. Meaning, cocaine is interacting somehow in the fathers abusing cocaine, and in turn is causing some type of shielding effect in male offspring specifically. Though this research controlled for environmental factors and only studied the effect of cocaine without it’s interaction with other drugs, something impossible to do with humans, unlike human genetic studies, however, this study was not correlational. Something to think about.
Questions to think about:What is going on neurologically in the fathers abusing cocaine? And why is this protective effect sex specific?
Vassoler, F.M., White, S.L., Schmidt, H.D., Sadri-Vakili, G., and Pierce, R.C. (2013) Epigenetic Inheritance of a Cocaine Resistance Phenotype. Nat Neurosci.16(1): 42-47. doi:10.1038/nn.3280.
One thought on “Is it Possible to Inherit a Resistance to Cocaine?”
I love epigenetics; I think that as a topic of research, epigenetics is so incredible and rich with potential. But its implications are more than a little scary. It seems that study after study finds that eating this causes metal deficiencies in our children or being exposed to that during the third trimester of pregnancy causes higher cortisol levels in the next generation. It appears that our DNA is less set in stone than we thought and is actually very sensitive to environmental factors. In reality, 60 days is really not that long for such a definite change and a change that is heritable. Another interesting point is that for most of the work on epigenetics that I have come across, the emphasis has been put on events that occur to the mother while she is pregnant. This study shows that a significant effect in children occurs because of something the father rat did before he mated with a healthy female. And while this effect turns out to increase BDFN and therefore lower cocaine administration, the implications of this study are immense. So does that mean I should convince my future husband to self-administer cocaine to himself so that our sons will inherit a resistance to cocaine? Probably not, though this is definitely a fascinating topic.