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Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus

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Abstract

Rationale

Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation.

Objectives

The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21 h/day, 4 days) with intermittent periods of deprivation (3 days) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1 h/day, 4 days) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session.

Results

Limited- and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration.

Conclusions

These findings demonstrate that extended versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to maladaptive addiction-like behaviors dependent on the hippocampus.

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Acknowledgments

Funds from grants DA022473, AA020098, and AA06420 (CDM) and DA004398 (GFK) from the National Institute of Health and the Pearson Center for Alcoholism and Addiction Research supported the study. We acknowledge the technical assistance of Anne Phan-Huy from University of California San Diego, Jan Kirby Zabala from the Life Sciences Summer Internship Program at The Scripps Research Institute, and Ariel Feifel for assistance with processing brain tissue and immunohistochemistry. We appreciate the technical support of Elena Crawford for immunohistochemical analyses and StereoInvestigator and the editorial assistance of McKenzie Fannon. This is publication number 26032 from The Scripps Research Institute.

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Correspondence to Chitra D. Mandyam.

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Ami Cohen and Matthew T. Soleiman equally contributed to this article.

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Cohen, A., Soleiman, M.T., Talia, R. et al. Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus. Psychopharmacology 232, 453–463 (2015). https://doi.org/10.1007/s00213-014-3685-0

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