title: Ethanol-induced Fos immunoreactivity in the extended amygdala and hypothalamus of the rat brain: focus on cholinergic interneurons of the nucleus accumbens.
abstract: BACKGROUND
  The primary goal of this study was to investigate the effects of varying doses of ethanol on cellular activation, as measured by Fos immunoreactivity, in brain areas that have been implicated in the reinforcing and anxiolytic effects of substance abuse and dependence, namely, the extended amygdala and hypothalamus. Specific regions examined included the central nucleus of the amygdala, bed nucleus of the stria terminalis, substantia innominata, and nucleus accumbens of the extended amygdala, as well as the paraventricular nucleus of the hypothalamus. The cholinergic interneurons of the nucleus accumbens were of particular interest, because these cells have recently been reported to play a pivotal role in substance abuse.
  
  
  METHODS
  Adult Sprague-Dawley rats underwent 10 days of handling and 5 days of habituation. Animals then received an injection of saline or 0.5, 1, or 2 g/kg of ethanol. Rats were perfused 2 hr after the injections, and brain sections were processed for single Fos or dual Fos/choline acetyltransferase immunolabeling procedures. The number of Fos-positive neurons was calculated from a 0.45-mm sample area from each of the brain regions examined.
  
  
  RESULTS
  A dose of 2 g/kg of ethanol significantly increased the number of Fos-immunoreactive neurons in the central nucleus of the amygdala by 149%, in the shell nucleus accumbens by 80%, and in the paraventricular nucleus of the hypothalamus by 321%. Additionally, 1 g/kg of ethanol significantly increased the percentage of Fos-immunoreactive cholinergic neurons in the nucleus accumbens by 59%.
  
  
  CONCLUSIONS
  The findings reported in this study reveal region-specific and dose-dependent changes in Fos immunoreactivity in the extended amygdala and hypothalamus and, more specifically, an increase in neuronal activation of cholinergic cells in the shell nucleus accumbens. These findings contribute to our current knowledge of the brain areas and cellular microcircuits involved in the underlying basis of substance abuse and dependence.
authors.affiliation: Department of Psychology, University of Texas at Austin, Austin, Texas 78712-0187, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Herring
authors.forename: R Dayne
authors.initials: RD
authors.lastname: Mayfield
authors.forename: Marguerite C
authors.initials: MC
authors.lastname: Camp
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Alcantara
mesh_terms: D000679:Amygdala / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002799:Cholinergic Fibers / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol