In the 12th episode of Fresh Perspectives with Amara Davis, the Loving Mind Institute discusses with first author Dr. Marta Pratelli, University of California San Diego, the recently published work entitled “Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits”. This interview with Dr. Marta Pratelli highlights groundbreaking research on neurotransmitter switching in the brain and its link to cognitive deficits caused by drug use. Dr. Pratelli’s research, conducted in Dr. Nicholas Spitzer’s lab, focuses on an often overlooked form of brain plasticity where neurons can change the type of neurotransmitter they express.
The study also explored pharmacological reversal using clozapine, an antipsychotic known to improve cognitive symptoms in schizophrenia- a condition that shares some cognitive deficit features with addiction models. Although clozapine has limitations due to side effects, the findings provide proof of principle that targeting neurotransmitter switching pathways could inspire new, safer treatment for substance use disorder.
By identifying how environmental factors, such as intaking mind-altering substances, can induce neurotransmitter switching with impact on cognitive function, we gain a deeper understanding of neurobiology that encourages further study into non-invasive stimulation methods that can be combined with behavioral-environmental approaches to treat addiction-related cognitive deficits and potentially other causes of cognitive dysfunction. Overall, this research broadens our understanding of brain plasticity in addiction and other conditions, elucidating an understudied mechanism, with exciting therapeutic potential and promising public health benefit at large.
Public Interest: This work reveals a reversible mechanism underlying memory and cognitive impairments associated with addiction, shifting the focus away from permanent neuronal loss towards adaptive changes in brain function. This opens new possibilities for therapeutic interventions that could restore cognitive abilities in affected individuals.
Innovation in Research: A major innovative aspect of this research is demonstrating that transmitter switching is necessary for the emergence of drug-induced memory and cognitive deficits. By preventing the neurotransmitter change through either genetic manipulation or chemogenetic inhibition of neuronal activity, the researchers were able to block the cognitive impairments. Furthermore, they showed that these changes are not due to neuronal death but represent an adaptive, reversible functional shift. This is significant because it suggests cognitive deficits from drug abuse might be treatable rather than permanent.
Key Research Findings: Analogous to traffic lights switching colors and thereby changing the flow of traffic, neurons can switch from excitatory to inhibitory signaling in response to environmental stimuli, including repeated drug exposure. This neurotransmitter switching was shown to occur in the prefrontal cortex of mice after exposure to the drugs, PCP and methamphetamine. Further supporting this mechanism of neural plasticity, neurotransmitter switching to GABA expression was also observed under substance-free induction by stimulating dopamine release, which the researchers used to model the effects of addiction. The reversibility of this neurotransmitter switching holds exciting therapeutic potential and promising health benefit for families, friends, and society at large.
To see Amara’s full Interview with Dr. Marta Pratelli on her research advancing our understanding of addiction, cognition, and brain recovery, view the video below or on the LMI YouTube Channel:
Pratelli, M., Hakimi, A.M., Thaker, A. et al. Drug-induced change in transmitter identity is a shared mechanism generating cognitive deficits. Nat Commun 15, 8260 (2024). https://doi.org/10.1038/s41467-024-52451-x