The consequences of ongoing drug abuse can appear in various forms. These include memory loss and diminished cognitive abilities, which can last for many years. Researchers at the University of California San Diego have pinpointed a specific mechanism in the brain that leads to cognitive issues caused by drugs.
The consequences of ongoing drug abuse can appear in various forms. These include memory loss and diminished cognitive abilities, which can last for many years. Researchers at the University of California San Diego have pinpointed a specific mechanism in the brain that leads to cognitive issues caused by drugs.
Scientists from the Department of Neurobiology, School of Biological Sciences, explored how both methamphetamine and phencyclidine (PCP or “angel dust”), which impact distinct targets in the brain, can produce similar declines in cognitive function. How is it possible that similar memory issues arise from drugs that affect the brain in different ways?
The findings from this study, directed by Assistant Project Scientist Marta Pratelli in Professor Nicholas Spitzer’s lab, are published in Nature Communications. The research revealed that both meth and PCP caused neurons to alter their communication patterns through a phenomenon referred to as neurotransmitter switching.
Neurotransmitter switching represents a type of brain plasticity, a growing field of study that looks into how the brain adjusts its structure and function based on experiences. Recently, Spitzer and his team have also discovered the roles of neurotransmitter switching in conditions like autism spectrum disorder, post-traumatic stress disorder, and even during exercise.
By studying the cerebral cortex of mice, the researchers observed that both meth and PCP triggered a transition from the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the same neurons located in the prelimbic region, which is part of the frontal cortex associated with executive functions. This neurotransmitter switch was found to correlate with poorer performance in memory tasks, as the mice treated with drugs performed better when GABA expression was inhibited.
Additional experiments demonstrated that even after being exposed to the drugs multiple times, the scientists could reverse the neurotransmitter switch using molecular techniques to lower the brain’s electrical activity or applying clozapine, an antipsychotic medication. Both methods led to the restoration of memory performance in the mice during cognitive tests.
“These findings suggest that targeted adjustments in neuronal activity could potentially help alleviate some adverse effects of chronic drug abuse,” Pratelli stated.
In their latest research, the scientists found that an increase in dopamine release—a neurotransmitter associated with reward—and heightened electrical activity in neurons of the cerebral cortex were essential for the neurotransmitter switch to occur.
“This research uncovers a common and reversible mechanism that governs the emergence of cognitive deficits following exposure to various drugs,” Spitzer commented.
The researchers point out in their publication that gaining a better understanding of the brain functions associated with memory loss due to drug use could pave the way for developing new treatments, potentially aiding in the therapy not just for meth and PCP misuse but for other related disorders as well.
The team included Marta Pratelli, Anna Hakimi, Arth Thaker, Hyeonseok Jang, Hui-quan Li, Swetha Godavarthi, Byung Kook Lim, and Nicholas Spitzer. The study received funding from the National Institute on Drug Abuse (R21 CEBRA grant DA048633; and R21 DA050821) and the Overland Foundation.
