Sustained drug abuse can lead to persistent memory loss and cognitive decline. Neurobiologists at the University of California San Diego have discovered a brain mechanism responsible for these drug-induced cognitive impairments as published in Nature Communications (1^✔ ✔Trusted Source
Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits

Go to source

).

Scientists in the Department of Neurobiology, School of Biological Sciences, investigated how methamphetamine and phencyclidine (PCP or “angel dust”), which take effect by activating different targets in the brain, induce a similar reduction in cognitive ability.

How could the same difficulties in memory emerge in response to drugs that trigger different actions in the brain?

The results of this investigation were led by Assistant Project Scientist Marta Pratelli in Professor Nicholas Spitzer’s laboratory.

They showed that meth and PCP caused neurons to change the way they communicate through a process known as neurotransmitter switching.

Neurotransmitter switching is a form of brain plasticity, an evolving area of research investigating how the brain changes function and structure in response to experience.

In recent years, Spitzer and his colleagues have also identified roles for neurotransmitter switching in autism spectrum disorder, post-traumatic stress disorder, and exercise.

Brain Mechanism Behind Drug-Induced Cognitive Decline

Examining the cerebral cortex of mice, the investigators found that meth and PCP each caused a switch from the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the same neurons in the prelimbic region, an area of the frontal cortex involved in executive functions.

This switch was linked to a decrease in memory task performance since drug-treated mice performed well in the tasks when the expression of GABA was blocked.

Further experiments showed that even after repeated exposure to the drugs, the researchers were able to reverse this neurotransmitter switch using molecular tools to locally decrease the brain’s electrical activity or using clozapine, an antipsychotic drug.

Each of these treatments reversed the memory loss, restoring the performance of mice in the cognitive tasks.

“These results suggest that targeted manipulation of neuronal activity may be used to ameliorate some of the negative effects of repeated drug abuse,” said Pratelli.

In this new study, the researchers found that a drug-induced increase in the release of dopamine, a neurotransmitter involved in reward, and an increase in the electrical activity of neurons in the cerebral cortex, were required to produce the neurotransmitter switch.

“This study reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs,” said Spitzer.

The researchers note in their paper that a deeper understanding of brain mechanisms tied to the loss of memory from drug use could boost prospects for new treatments, not only resulting in therapy for meth and PCP consumption but for other disorders as well.

Reference:

1. Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits
   – (https://www.nature.com/articles/s41467-024-52451-x)

Source-Newswise