title: Nicotine withdrawal increases stress-associated genes in the nucleus accumbens of female rats in a hormone-dependent manner.
abstract: BACKGROUND
  Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated.
  
  
  METHODS
  Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45-46). On PND 60, they received sham surgery (controls) or were prepared with nicotine pumps. Fourteen days later, half of the rats had their pumps removed (nicotine withdrawal) and the other half received sham surgery (nicotine exposure). Twenty-four hours later, the rats were tested for anxiety-like behavior using the elevated plus maze and light/dark transfer procedures. The NAcc was then dissected for analysis of several genes related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for dopamine (Drd1 and Drd2) and estradiol (Esr2).
  
  
  RESULTS
  During withdrawal, intact females displayed an increase in anxiety-like behavior in both tests and CRF, UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in CRF-BP. This pattern of results was absent in OVX females.
  
  
  CONCLUSIONS
  Nicotine withdrawal produced an increase in anxiety-like behavior and stress-associated genes in intact females that is distinct from changes produced by nicotine exposure. The latter effects were absent in OVX females, suggesting that stress produced by withdrawal is ovarian-hormone mediated. These findings have important implications towards understanding tobacco use liability among females.
authors.affiliation: Department of Psychology, University of Texas at El Paso, El Paso, TX.
authors.forename: Oscar V
authors.initials: OV
authors.lastname: Torres
authors.affiliation: Department of Psychology, University of Texas at El Paso, El Paso, TX.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pipkin
authors.affiliation: Department of Psychology, University of Texas at El Paso, El Paso, TX.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ferree
authors.affiliation: Department of Psychology, University of Texas at El Paso, El Paso, TX.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Carcoba
authors.affiliation: Department of Psychology, University of Texas at El Paso, El Paso, TX lodell@utep.edu.
authors.forename: Laura E
authors.initials: LE
authors.lastname: O'Dell
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005260:Female; D005783:Gender Identity; D018782:Maze Learning / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking; D013312:Stress, Physiological / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D009538:Nicotine; D003346:Corticotropin-Releasing Hormone