title: Adolescent nicotine-induced dendrite remodeling in the nucleus accumbens is rapid, persistent, and D1-dopamine receptor dependent.
abstract: Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent.
authors.affiliation: Department of Psychology, George Mason University, Fairfax, USA. dehlinge@gmu.edu.
authors.forename: D G
authors.initials: DG
authors.lastname: Ehlinger
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Bergstrom
authors.affiliation: Department of Psychology, George Mason University, Fairfax, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Burke
authors.affiliation: Department of Psychology, George Mason University, Fairfax, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Fernandez
authors.affiliation: Department of Psychology, George Mason University, Fairfax, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: McDonald
authors.affiliation: Department of Psychology, George Mason University, Fairfax, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Smith
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D009538:Nicotine
keywords: Adolescence; D1 receptor; Dendrite morphology; Dendritic spine; Dopamine; Nicotine