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

Abstract

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.

Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

“…Nicotine's effects on nicotinic acetylcholine receptors and regional blood flow in the brain are complex, important, and incompletely understood. Chronic exposure is known to change the structural plasticity of the brain [36,37]. Nicotinic receptor activation acutely causes the release of dopamine, glutamate, norepinephrine, acetylcholine, serotonin, B-endorphin, and gamma-aminobutyric acid (GABA), and acute smoking cessation causes a state of ''subnormal release of dopamine and other neurotransmitters [38].''…”

Adolescent nicotine induces persisting changes in development of neural connectivity

“…Results revealed that adolescent nicotine resulted in increased branching complexity of basilar dendrites of neurons with complex apical tufts, while adult dosing induced increasing branching only in those with simple tufts. Thus, we concluded that both adolescent and adult nicotine induce growth of dendrites in mPFC neurons, but the effects are on different populations of neurons, with putatively different connectivity, at different ages (Bergstrom et al, 2008). Unlike the differences between MSNs and aspiny cell types, where MSNs are clearly part of the reinforcement system and aspiny neurons are not, classification of layer 5 pyramidal neurons by projection field or function is less clear.…”

Long-Lasting Cognitive Deficits Resulting from Adolescent Nicotine Exposure in Rats

“…Moreover, it has been suggested that in addition to a different timing, there might be a different developmental mechanism between mPFC and Acb, as dopamine D1 and D2 receptors in the mPFC undergo overproduction, which subsequently leads to massive pruning during adolescence, whereas Acb dopamine receptors show overproduction at P40, but virtually no pruning occurs (Andersen et al, 2000). Also, adolescent nicotine exposure has long-term effects on morphology of a subpopulation of pyramidal neurons in the mPFC, seen as an increase in dendritic length of complex pyramidal cells (Bergstrom et al, 2008). These persistent changes induced by adolescent exposure to nicotine may be brought about by the increased induction of plasticity-associated genes, which were found to be specifically upregulated in the mPFC of animals treated with nicotine during adolescence (Schochet et al, 2005).…”