Rapidly emerging adolescent nicotine-induced dendritic remodeling is D1-dopamine receptor dependent




Ehlinger, Daniel Gavin

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Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell of the rat. While nicotine-induced dendritic remodeling has frequently been described as persistent, no time-course studies have assessed whether dendritic remodeling is present immediately following nicotine exposure or if dendritic remodeling develops over an extended drug-abstinent period. Furthermore, the specific neuropharmacological mechanisms through which nicotine exposure may alter dendrite morphology is relatively unknown. To address these questions, Sprague-Dawley rats were co-administered subcutaneous injections of either saline or the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05mg/kg) 20 minutes prior to the subcutaneous injection of either saline or nicotine (0.5 mg/kg) beginning on postnatal day (P) 28. Injections were administered every other day for 8 total injection days ending on P42. Brains were then processed for Golgi-Cox staining either 1-day (P43) or 21-days (P63) following drug exposure. Dendrites from MSNs were digitally reconstructed in three-dimensions, and dendritic spine density was assessed on ~40&mum segments of terminal branches. Our results show that (1) chronic adolescent nicotine exposure rapidly induces the formation of new dendritic branches and dendritic spines on NAcc Shell MSNs by P43, (2) nicotine-induced dendritic remodeling, but not increased spine density, is maintained through an extended abstinent period until at least P63, (3) the co-administration of SCH-23390 prior to each nicotine injection blocked nicotine-induced dendritic remodeling of MSNs when measured at both P43 and P63, suggesting that nicotine-induced formation of new dendritic branches is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Collectively, these results suggest that chronic adolescent nicotine-induced dendritic remodeling of NAcc Shell MSNs rapidly develops during the course of nicotine exposure, and that nicotine-induced D1DR activation has a specific influence on the formation of new dendritic branches, but not dendritic spines. These data highlight the influence of chronic nicotine on adolescent brain development and show that long-lasting, nicotine-induced, dendritic remodeling is D1DR dependent in the NAcc shell.



Neurosciences, Physiological psychology, Animal behavior, Adolescence, D1 receptor, Dendrite morphology, Dendritic spines, Dopamine, Nicotine