Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice.

Developmental tobacco or nicotine exposure is associated with various adverse outcomes in human and preclinical studies, respectively. For example, perinatal nicotine exposure in mice causes morphologic changes in neurons across sensory and motor cortices and results in impairments in sensory learning. However, the effects of developmental nicotine exposure on motor learning have not been reported. To determine whether nicotine-induced changes in behavior extend to motor tasks, we provided female C57Bl/6 dams with nicotine drinking water (200 μg/ml in 2% saccharin), or vehicle (2% saccharin), a standard paradigm to expose pups to nicotine in utero and postnatally through lactation. Male and female pups were subsequently tested in adulthood in a single-pellet reaching task with millet seeds, and also tested for gross motor function and feeding behavior. We found that male, but not female, mice exposed to nicotine throughout early development demonstrated impaired learning of single-seed reaching. Nicotine-treated animals did not differ from control animals in gross motor performance or millet seed intake, although female mice consumed more millet seeds than male mice when reaching was not required. These studies show that nicotine exposure during development can impair behavior in a skilled motor task that depends on cortical synaptic plasticity, and that this effect is sex-dependent.