title: Blunted opiate modulation of hypothalamic-pituitary-adrenocortical activity in men and women who smoke.
abstract: OBJECTIVE
  To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers.
  
  
  METHODS
  Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test.
  
  
  RESULTS
  Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers.
  
  
  CONCLUSIONS
  We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers.
authors.affiliation: Department of Behavioral Sciences, University of Minnesota Medical School, Duluth, Minnesota 55812, USA. malabsi@umn.edu
authors.forename: Mustafa
authors.initials: M
authors.lastname: al'Absi
authors.forename: Lorentz E
authors.initials: LE
authors.lastname: Wittmers
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.forename: Ruth
authors.initials: R
authors.lastname: Westra
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D012463:Saliva / Q000737:chemistry; D012737:Sex Factors; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology; D014029:Tobacco Use Disorder / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009271:Naltrexone; D009538:Nicotine; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
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