Blocking Enzyme in Brain’s Decision-Making Center Reduces Opioid Relapse: Study

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Researchers at the Medical University of South Carolina (MUSC) have made a significant discovery regarding the role of pyramidal neurons in the brain’s decision-making center in relation to relapse into drug seeking after heroin abstinence. Their findings, published in the Journal of Neuroscience, provide valuable insights into the effects of opioids on these neurons and may open doors to new treatment options.

The study, conducted using a rodent model, focused on the excitable activity of pyramidal neurons and its impact on relapse. The research team found that blocking the enzyme protein kinase A (PKA) restored normal excitable activity in the brain and subsequently reduced the urge to seek opioids.

Jacqueline McGinty, a professor of neuroscience at the university, explained that compulsive drug use often involves the loss of decision-making abilities and a susceptibility to environmental triggers associated with drug-taking. The team discovered that specific types of pyramidal neurons in the prelimbic prefrontal cortex, a region responsible for decision-making and behavioral control, undergo molecular and functional changes during heroin abstinence, disrupting normal brain function in this area.

The nucleus accumbens and the prelimbic cortex, two brain regions involved in cue-induced relapse, were the focal points of the study. The nucleus accumbens, which receives input from the prelimbic cortex and dopamine-releasing pathways, plays a crucial role in the desire to take substances associated with addictive drugs. Aberrant functioning of these pathways during abstinence contributes significantly to cue-induced relapse.

The researchers observed increased activity in the neurons connecting the prelimbic cortex to the nucleus accumbens during periods of abstinence, potentially driving relapse. By blocking PKA in the prelimbic cortex, the enzyme found to be more active during abstinence, the researchers were able to restore neuronal activity to normal levels. This restoration of control within the brain led to better behavioral control, resulting in decreased heroin seeking.

While the findings are promising, further research is necessary to fully understand the mechanisms involved and develop potential interventions. However, this study highlights the importance of targeting the excitable activity of pyramidal neurons in the brain’s decision-making center as a potential avenue for reducing relapse in individuals struggling with opioid addiction.

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