title: Nicotine and Resting-State Functional Connectivity: Effects of Intermittent Doses.
abstract: BACKGROUND
  It is unknown how the timing between doses might affect nicotine's impact on neural activity. Our objective was to examine how the interdose interval affects nicotine's impact on resting-state functional connectivity (rsFC).
  
  
  METHODS
  Adult male Sprague-Dawley rats were administered nicotine daily (0.4 mg/kg) over 6 days while control animals received saline vehicle. Functional magnetic resonance imaging was used to measure rsFC before and after a challenge dose of nicotine (0.4 mg/kg) delivered for the first time and 3, 6, 12, or 24hr after the previous dose.
  
  
  RESULTS
  As the interval between nicotine doses increased from 3 to 24hr, the strength of rsFC increased in some circuits, particularly the nucleus accumbens and prefrontal circuits, and decreased in others, namely the interpeduncular nucleus, hippocampus, caudoputamen, retrosplenial cortex, ventral tegmental, and the insular circuits.
  
  
  CONCLUSIONS
  These data indicate that the effect that nicotine has on the brain is affected by the amount of time that has passed since the previous dose. The effect on rsFC of cumulative doses is not additive. This may have important implications for the study of nicotine addiction as it implies that the same dose of nicotine might have a different impact on the brain depending on the time elapsed from the previous exposure.
authors: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA;
authors: Wei
authors: W
authors: Huang
authors: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA;
authors: Kelly
authors: K
authors: Tam
authors: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA;
authors: Janaque
authors: J
authors: Fernando
authors: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA;
authors: Meghan
authors: M
authors: Heffernan
authors: Jean
authors: J
authors: King
authors: Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA; Department of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester, MA difranzj@ummhc.org.
authors: Joseph R
authors: JR
authors: DiFranza
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking
chemical_list: D009538:Nicotine
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