title: Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA.
authors: Ami
authors: A
authors: Cohen
authors: Matthew T
authors: MT
authors: Soleiman
authors: Reneta
authors: R
authors: Talia
authors: George F
authors: GF
authors: Koob
authors: Olivier
authors: O
authors: George
authors: Chitra D
authors: CD
authors: Mandyam
mesh_terms: D000818:Animals; D016739:Behavior, Addictive; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D055495:Neurogenesis; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000473:pathology
chemical_list: D009538:Nicotine