Continuous nicotine administration produces selective, age-dependent structural alteration of pyramidal neurons from prelimbic cortex.

Emerging evidence indicates that adolescence represents a developmental window of enhanced nicotine-induced neuroplasticity in rat forebrain. However, whether nicotine produces age-dependent structural alteration of neurons from medial prefrontal cortex remains to be determined. We characterized the dendritic morphology of layer V pyramidal neurons from prelimbic cortex following adolescent (P29-43) or adult (P80-94) nicotine pretreatment. Nicotine administration was via osmotic pump [initial dose 2.0 mg/(kg day), free base]. Five weeks after drug administration concluded, brains were processed for Golgi-Cox staining and pyramidal neurons digitally reconstructed for morphometric analysis. Overall, nicotine pretreatment produced increased basilar, but not apical, dendritic length of pyramidal cells, a finding consistent with previous work using adult animals. Given the compelling evidence for morphologically distinct functional subtypes of cortical pyramidal neurons, we endeavored to determine whether nicotine-induced dendritic alteration was specific to putative structural subtypes. Neurons were segregated into two groups based on the extent of dendritic arbor at the distal portion of the apical tree (i.e., the apical tuft). The size of the apical tuft was quantitatively determined using principal component analysis. Cells with small and elaborate apical tufts were classified as simple and complex, respectively. We found that adult nicotine pretreatment produced increased basilar dendritic length and branch number in simple but not complex pyramidal cells. In contrast, adolescent nicotine pretreatment produced a modest but significant increase in basilar dendritic length in complex but not simple cells. These data suggest that nicotine alters dendritic morphology of specific subpopulations of pyramidal neurons and that the subpopulation affected is dependent on the age of drug exposure.