Early exposure to nicotine modifies neurons, predisposes the brain to subsequent dependence

Neonatal exposure to nicotine modifies the reward circle in the brains of newborn mice, thus increasing their preference for the drug in adulthood, report researchers at the Faculty of Medicine of the United States. University of California at San Diego in a study published April 24, 2019 in Biological Psychiatry.

A team of scientists from the University of San Diego School of Medicine, led by lead author Davide Dulcis, Ph.D., badociate professor in the Department of Psychiatry, along with colleagues from Veterans Affairs San Diego Healthcare System and Michigan State University, found that exposure to nicotine in the first few weeks of life (through maternal lactation) induced a variety of long-term neurological changes in young mice.

Specifically, it caused a form of neuroplasticity that resulted in an increase in the number of modified neurons in the ventral tagmental region (VTA) of the brain as a result of new exposure to nicotine at age adult. The biochemistry of these neurons was different from that of other neurons, including greater receptivity to nicotine and greater likelihood of subsequent addictive behavior.

"Previous studies had previously shown that maternal smoking and early postnatal exposure to nicotine were badociated with a change in children's behavior and a heightened propensity to addiction in humans," Dulcis said. . "This new research in mice helps elucidate the mechanisms explaining how and why.Neonatal exposure to nicotine prepares VTA neurons to a fate that they would not normally have taken, making them more sensitive to the effects of nicotine when animals are re-exposed to nicotine later in life. "

When young neurons are exposed to a foreign drug, such as nicotine, they create a molecular "memory," said lead author, Ben Romoli, Ph.D., a postdoctoral fellow at Dulcis Lab. By increasing the expression of nicotine receptors and the molecular marker Nurr1, a protein that is normally found only in dopaminergic neurons, these neurons expressing GABA and glutamate gain the "promptitude" to go through. to a dopaminergic program when they are properly motivated by nicotine. adult.

"We found that when the same animals are exposed to nicotine in adulthood, a fraction of these" primed "glutamatergic neurons in the reward center begin to express the genes needed for dopamine production. increased dopamine in the system generates improved reward responses leading to an increase in nicotine preference. "

Dulcis said that the discovery of the molecular mechanism and identity of the neural network involved was an important step towards a more complete understanding of how a complex condition such as dependence might work.

"Our preclinical work has identified new cellular and molecular targets that can guide future clinical studies to refine treatment strategies," said Dulcis. "Because we have found that this form of nicotine-induced neuroplasticity facilitates the dependence on other addictive substances, such as ethanol in the adult, the discovery of the mechanism contributing to increased susceptibility." addiction offers the rare opportunity to discover new ways to interfere with the mechanism of drug mediation, plasticity and avoid negative consequences on the reward seeking behavior in the adult. "

The researchers said the results were highly relevant to tobacco control programs because the neonatal effect of nicotine observed in the study was induced by exposure due to maternal lactation and that the ## EQU1 ## Current state and local policies did not regulate this particular type of nicotine intake.

"We plan to determine whether early exposure to other commonly used drugs, such as alcohol, marijuana or recently legalized opioids, may induce similar adaptations of the reward center that affects drug preferences in adulthood, "said Dulcis. "It would also be interesting to determine if this form of neurotransmitter plasticity is inducible or reversible at different stages of life, while the brain is still extremely plastic and subject to addiction, as in adolescence."

Scientists are also studying applications to improve the behavioral performance of animal models for diseases badociated with a loss of dopaminergic neurons, such as Parkinson's disease.