Nicotine on the developing brain

Abstract

Developmental periods such as gestation and adolescence have enhanced plasticity leaving the brain vulnerable to harmful effects from nicotine use. Proper brain maturation and circuit organization is critical for normal physiological and behavioral outcomes. Although cigarette smoking has declined in popularity, noncombustible nicotine products are readily used. The misperceived safety of these alternatives lead to widespread use among vulnerable populations such as pregnant women and adolescents. Nicotine exposure during these sensitive developmental windows is detrimental to cardiorespiratory function, learning and memory, executive function, and reward related circuitry. In this review, we will discuss clinical and preclinical evidence of the adverse alterations in the brain and behavior following nicotine exposure. Time-dependent nicotine-induced changes in reward related brain regions and drug reward behaviors will be discussed and highlight unique sensitivities within a developmental period. We will also review long lasting effects of developmental exposure persisting into adulthood, along with permanent epigenetic changes in the genome which can be passed to future generations. Taken together, it is critical to evaluate the consequences of nicotine exposure during these vulnerable developmental windows due to its direct impact on cognition, potential trajectories for other substance use, and implicated mechanisms for the neurobiology of substance use disorders.

Keywords: Adolescence; E-cigarettes; Epigenetics; Prenatal; Tobacco; Transgenerational transmission.

Fig. 1.

Major nicotine-induced alterations within rodent brain during prenatal period. PFC, prefrontal cortex. NAc, nucleus accumbens. SN, substantia nigra. VTA, ventral tegmental area. PPTg, pedunculopontine nucleus. LDTg, laterodorsal tegmental. ROb, raphe obscurus. DA, dopamine.

Fig. 2.

Major nicotine-induced alterations within rodent during postnatal/perinatal period. Hipp, hippocampus.

Fig. 3.

Major nicotine-induced alterations within rodent brain during adolescent period. PFC, prefrontal cortex. NAc, nucleus accumbens. SN, substantia nigra. VTA, ventral tegmental area. DA, dopamine.

Fig. 4.

Multigenerational and transgenerational transmission of nicotine-induced effects. This diagram illustrates multigenerational transmission of effects following direct prenatal and perinatal nicotine exposure in F0 mothers. Transgenerational transmission effects, resulting without direct exposure to nicotine, are described in F2 generation from prenatal and perinatal exposure. Adolescent nicotine exposure in animals from both sexes elicits transgenerational effects in F1 and F2 offspring.