Our lab combines animal models of addiction with molecular biological techniques to study epigenetic mechanisms underlying addiction susceptibility.
Drug addiction is a massive public health concern that inflicts extensive burdens on our economy and society.
Each year about 65 million individuals are exposed to opioids.
Of these, about 13 million misuse or abuse these drugs.
Why are some individuals more susceptible to abuse drugs? The interaction between genome (genetic makeup) and environment shapes the development of psychiatric diseases, including Substance Use Disorder. The etiology of addiction has a large genetic component and epidemiological studies suggest that Substance Use Disorder is heritable. The other side of that coin are epigenetic processes, which can be broadly defined as environmental influences on gene expression.
The emergence of epigenetic studies has provided a concrete mechanism for the long-held idea that psychiatric diseases are caused by complex interactions between environmental and genetic factors. The rapid explosion of publications on this topic over the past decade has brought new hope for identifying novel therapeutic targets and treatments for addiction.
Using multigenerational animal models to delineate epigenetic mechanisms underlying addiction vulnerability.
We have developed a multigenerational model to study the influence of drug exposure on future generations. Based on epidemiological data, our prediction was that the offspring of drug-exposed sires (fathers) would be more susceptible to develop addiction-like traits.
We are interested in two major questions:
- (1) How is the information passed on from fathers to their offspring? How can paternal drug taking alter the germline epigenome (sperm)? Which germline epigenetic reprogramming events are critical for shaping development toward addiction vulnerability in the next generation?
- (2) What has changed in the brain of the offspring produced by drug-treated fathers? What are the functionally relevant neuro-epigenetic processes that increase addiction-like behavior in the first generation progeny?
Influence of paternal drug exposure on memory in the next generation
Some of the most debilitating consequences of addiction are the memory and cognitive deficits that often accompany chronic drug taking. Cognitive impairments are predictive of treatment retention and outcome, which is why some of the therapeutic strategies have focused on ameliorating drug-related neurocognitive insufficiencies. Clinical studies indicate that maternal drug exposure has deleterious effects on attention and impulsivity in offspring. However, the effect of paternal drug taking on cognitive function in offspring remains largely unstudied. Our lab uses the same multi-generational models of drug exposure to examine the long-term consequences of paternal drug taking on offspring memory.
Our published work on this topic:
Wimmer ME, Briand LA, Fant B, Guercio LA, Arreola AC, Schmidt HD, Sidoli S, Han Y, Garcia BA, Pierce RC (2017) Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny. Molecular Psychiatry. 22(11):1641-1650, PMCID PMC5568460
Molecular underpinnings of relapse
Substance Use Disorder is a chronic relapsing disease with high relapse rates that are on par with other prevalent diseases such as hypertension and asthma. A better understanding of the molecular mechanisms underlying drug relapse is needed to improve therapies for the treatment of addiction. Our lab relies on the drug self-administration and reinstatement model to examine the molecular pathways involved in drug seeking behavior and drug relapse.