Research from the Perelman School of Medicine at the University of Pennsylvania and Massachusetts General Hospital (MGH) reveals that sons of male rats exposed to cocaine are resistant to the rewarding effects of the drug, suggesting that cocaine-induced changes in physiology are passed down from father to son. The findings are published in the latest edition of Nature Neuroscience.
"We know that genetic factors contribute significantly to the risk of cocaine abuse, but the potential role of epigenetic influences – how the expression of certain genes related to addiction is controlled – is still relatively unknown," said senior author R. Christopher Pierce, PhD, associate professor of Neuroscience in Psychiatry at Penn.
"This study is the first to show that the chemical effects of cocaine use can be passed down to future generations to cause a resistance to addictive behavior, indicating that paternal exposure to toxins such as cocaine can have profound effects on gene expression and behavior in their offspring."
In the current study, the team used an animal model to study inherited effects of cocaine abuse. Male rats self-administered cocaine for 60 days, while controls were administered saline. The male rats were mated with females that had never been exposed to the drug. To eliminate any influence that the males' behavior would have on the pregnant females, they were separated directly after they mated.
The rats' offspring were monitored to see whether they would begin to self-administer cocaine when it was offered to them. The researchers discovered that male offspring of rats exposed to the drug, but not the female offspring, acquired cocaine self-administration more slowly and had decreased levels of cocaine intake relative to controls. Moreover, control animals were willing to work significantly harder for a single cocaine dose than the offspring of cocaine-addicted rats, suggesting that the rewarding effect of cocaine was decreased.
In collaboration with Ghazaleh Sadri-Vakili, MS, PhD, from MGH, the researchers subsequently examined the animals' brains and found that male offspring of the cocaine-addicted rats had increased levels of a protein in the prefrontal cortex called brain-derived neurotrophic factor (BDNF), which is known to blunt the behavioral effects of cocaine.
"We were quite surprised that the male offspring of sires that used cocaine didn't like cocaine as much," said Pierce. "While we identified one change in the brain that appears to underlie this cocaine resistance effect, there are undoubtedly other physiological changes as well and we are currently performing more broad experiments to identify them. We also are eager to perform similar studies with more widely used drugs of abuse such as nicotine and alcohol."
The findings suggest that cocaine use causes epigenetic changes in sperm, thereby reprogramming the information transmitted between generations. The researchers don't know exactly why only the male offspring received the cocaine-resistant trait from their fathers, but speculate that sex hormones such as testosterone, estrogen and/or progesterone may play a role.
The first author of the paper, Fair M. Vassoler, PhD, is a recent graduate of the Penn neuroscience graduate group. Other investigators from Penn who contributed to this work include Samantha L. White and Heath D. Schmidt.
The work was supported by grants from the National Institutes of Health (R01 DA15214, R01 DA22339, R01 DA33641, K02 DA18678, K01 DA30445, F31 DA31535, T32 DA28874 and T32 MH86599).
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.
Jessica Mikulski | EurekAlert!
The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung
A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences