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Institution: University of California, San Diego
Investigator(s): Davide Dulcis, Ph.D.
Award Cycle: 2018 (Cycle 27) Grant #: 27IR-0020 Award: $926,775
Subject Area: Neuroscience of Nicotine Addiction and Treatment
Award Type: High Impact Research Project Award

Initial Award Abstract

Despite extensive public health campaigns and the new California law 21 aimed at lowering tobacco use, 14% of the adult American population still report to be a regular smoker. Nicotine, the principal neuroactive component of tobacco, acts on the brain’s reward system, affecting reward-seeking behaviors and inducing addiction. Using mice as a model system, we will investigate how exposure of newborns to nicotine leads to changes in the developing brain that can permanently alter reward-processing and promote substance abuse in the adult. Our preliminary data showed that newborn nicotine exposure induces significant changes in certain neurons that do not normally produce dopamine, a neurotransmitter (chemical released from neurons) that plays a role in addiction. Those neurons acquire the ability to produce dopamine and thereby become prepared to respond to nicotine exposure and affect nicotine preference in the adult.  In this study, we will uncover the molecular and cellular mechanisms by which nicotine-induced changes during brain development lead to an increase in the number of dopamine-producing neurons in the adult brain. The study of such neurotransmitter plasticity could greatly contribute to our understanding why adolescents and adults who were exposed to nicotine early in life show an increased susceptibility to nicotine addiction. Importantly, nicotine-induced neuroplasticity could facilitate addiction to other addictive substances, such as alcohol, as well. Since brains of newborn mice are developmentally similar to those of human third trimester fetuses, our findings should further stimulate research into the use of nicotine-patches or electronic cigarettes by pregnant women and the potential long-lasting effects that it could have on their babies, as the use of these nicotine delivery devices may expose the fetus to nicotine concentrations comparable to those employed in this study.