Sex-dependent effects of nicotine on the developing brain.

The use of tobacco products represents a major public health concern, especially among women. Epidemiological data have consistently demonstrated that women have less success quitting tobacco use and a higher risk for developing tobacco-related diseases. The deleterious effects of nicotine are not restricted to adulthood, as nicotinic acetylcholine receptors regulate critical aspects of neural development. However, the exact mechanisms underlying the particular sensitivity of women to develop tobacco dependence have not been well elucidated. In this mini-review, we show that gonadal hormone-mediated sexual differentiation of the brain may be an important determinant of sex differences in the effects of nicotine. We highlight direct interactions between sex steroid hormones and ligand-gated ion channels critical for brain maturation, and discuss the extended and profound sexual differentiation of the brain. We emphasize that nicotine exposure during the perinatal and adolescent periods interferes with normal sexual differentiation and can induce long-lasting, sex-dependent alterations in neuronal structure, cognitive and executive function, learning and memory, and reward processing. We stress important age and sex differences in nicotine's effects and emphasize the importance of including these factors in preclinical research that models tobacco dependence.