Neonatal exposure to nicotine alters the reward circuity in the brains of newborn mice, increasing their preference for the drug in later adulthood, report researchers at University of California San Diego School of Medicine in a published study.
A
stained micrograph of a mouse purkinje neuron, a type of brain cell
that releases the GABA neurotransmitter, and which is affected by
nicotine exposure.
MEDIA CONTACT
Available for logged-in reporters only
SECTION
TYPE OF ARTICLE
Research Results
Newswise — Neonatal exposure to nicotine alters the
reward circuity in the brains of newborn mice, increasing their
preference for the drug in later adulthood, report researchers at
University of California San Diego School of Medicine in a study
published “in press” April 24, 2019 in
Biological Psychiatry.
A
UC San Diego School of Medicine team of scientists, headed by senior
author Davide Dulcis, PhD, associate professor in the Department of
Psychiatry, with colleagues at 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 increased numbers
of modified neurons in the ventral tagmental area (VTA) of the brain
following nicotine re-exposure as adults. These neurons displayed a
different biochemistry than other neurons, including greater receptivity
to nicotine and a greater likelihood of subsequent addictive behavior.
“Previous
studies have already shown that maternal smoking and early postnatal
exposure to nicotine are associated with altered children’s behaviors
and an increased propensity for drug abuse in humans,” said Dulcis.
“This new research in mice helps elucidate the mechanisms of how and
why. Neonatal nicotine exposure primes VTA neurons for a fate they
normally would not have taken, making them more susceptible to the
effects of nicotine when the animals are again exposed to nicotine later
in life.”
When young neurons are exposed to a foreign drug,
such as nicotine, they create a molecular “memory,” said first author
Ben Romoli, PhD, a postdoctoral fellow in the
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 GABA- and Glutamate-expressing neurons acquire the
“readiness” to switch to a dopaminergic program when properly motivated
by nicotine in the 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 begins to express genes
required to produce dopamine. More dopamine in the system generates
enhanced reward responses that lead to increased nicotine preference.”
Dulcis
said uncovering the molecular mechanism and the identity of the
neuronal network involved is an important step toward a fuller
comprehension of how a complex condition like addiction may work.
“Our
pre-clinical work identified new cellular and molecular targets that
may guide future clinical studies to refine treatment strategies,”
Dulcis said. “Because we found that this form of nicotine-induced
neuroplasticity facilitates addiction to other addictive substances,
such as ethanol in adults, uncovering the mechanism contributing to
increased addiction susceptibility offers the rare opportunity to
discover new ways to interfere with the mechanism of drug-mediated
plasticity and prevent the negative consequences on reward-seeking
behavior in the adult.”
Researchers said the results are highly
relevant to tobacco control programs because the neonatal nicotine
effect observed in the study were induced by exposure through maternal
lactation and current state and local policies do not regulate this
particular type of nicotine intake.
“We are planning to
investigate whether early exposure to other commonly used drugs, such as
alcohol or recently legalized marijuana or opioids, can induce similar
adaptations of the reward center that affects drug preferences in
adulthood,” said Dulcis. “It would be also interesting to determine
whether this form of neurotransmitter plasticity is inducible or
reversible at different stages of life when the brain is still extremely
plastic and prone to drug addiction, like in adolescence.”
The
scientists are also investigating applications aimed at improving the
behavioral performance of animal models for diseases associated with a
loss of dopaminergic neurons, such as Parkinson’s disease.
Co-authors
of the study include: Adrian F. Lozada and Darwin K. Berg, UC San
Diego; Ivette M. Sandoval and Frederic P. Manfredsson, Michigan State
University; and Thomas S. Hnasko, UC San Diego and Veterans Affairs San
Diego Healthcare System.
Funding for this research came, in
part, from the National Institutes of Health, the Kavli Institute for
Brain and Mind (grant 2012-18), the Tobacco-Related Disease Research
Program (271R-0020) and the National Institute of Neurological Disorders
and Stroke (5R21NS098079).
