Opioids reduce the brain's ability to form and maintain synapses

Heroin exposure significantly reduces the levels of protein required for the development and maintenance of synapses in the brain, a preclinical study by researchers at the University of Buffalo revealed. The development of a relapse of addiction is directly related to the impact that the reduction of this protein, called drebrine, has on specific cells involved in the brain's fun / reward search pathways.

The UB research paper, one of the first to trace the pathophysiology of relapse dependence, was published online Sept. 12. Nature Communications.

The neurobiology of relapse

"Very little research has examined the molecular mechanisms of heroin relapse and there is almost nothing published about the specific cell types in which these changes occur," said David Dietz, Ph.D. .D., Senior author of the newspaper, director of the department. pharmacology and toxicology of the Jacobs School of Medicine and Biomedical Sciences at UB and faculty member of UB's neuroscience program.

"These findings have led to a better understanding of the neurobiology of opioid relapse and, combined with other discoveries, will hopefully provide treatment options to prevent relapse behaviors."

Most currently available treatments are alternative therapies, none of which take into account the fundamental changes in addiction and lead to a relapse, which remains an insoluble problem.

Dietz and his colleagues have focused much of their research on relapses after withdrawal and opioid dependence, as well as on the structural plasticity of the brain that they cause. He recently received more than $ 2 million from the National Institutes of Health (NIH) to continue his research on dung and other potential targets for drug treatment.

Drebrin was interesting because the loss of the protein had already been implicated in brain diseases, such as Alzheimer's disease and Down's syndrome.

"Since Drebrin is responsible for developing and maintaining synapses, we wondered if he was also involved in addiction, ultimately leading to a relapse," Dietz said.

In experiments on rodents, the UB team determined that exposure to heroin and morphine reduced drebrin levels in the nucleus accumbens, a key component of the path of the reward of the brain.

Synaptic rewiring

The researchers found that opioid exposure causes synaptic rewiring in this part of the brain, as well as a decrease in the drenditic spines, the protrusions of the neurons that play a key role in the transmission, l? learning and memory of neurons.

"Opiates fundamentally change the way the brain communicates with itself," Dietz said.

The researchers found that reducing drebrin levels is regulated by changes in the way an enzyme called HDAC2 facilitates access to DNA. In addition, the study demonstrates that these changes occur exclusively in a specific type of nucleus accumbens cells, called D1, which contains medium-spine neurons, the type of cells that make up this part of the reward center.

"Restoring drebrine to normal levels in these specific brain cells was enough to reduce relapse patterns," Dietz said.

The research provides a critical and uneducated review of the mechanisms behind addictive behaviors and relapses, which, combined with future studies, could lead to innovative and effective treatment for relapse prevention.

"Our lab is focused on improving our understanding of the neurobiology of addiction and relapse so that we can find the best way to target these pathways for future therapeutic use," Dietz said.