title: Neurosteroids in nicotine and morphine dependence.
abstract: BACKGROUND
  Neurosteroids are implicated in various stages of drug dependence, including the acquisition phase, tolerance, and withdrawal. The neurosteroid allopregnanolone is also able to substitute for drugs with abuse potential and possesses reinforcing properties.
  
  
  OBJECTIVE
  The effects of acute treatment with, and discontinuation of, chronic exposure to nicotine or morphine on the concentrations of allopregnanolone and its precursors, pregnenolone and progesterone, in the cerebral cortex and plasma of rats were investigated. The role of the hypothalamic-pituitary-adrenal (HPA) axis in, and the development of tolerance to, such effects were also examined.
  
  
  METHODS
  Nicotine or morphine was administered acutely or chronically, and withdrawal syndrome was induced by spontaneous discontinuation of drug treatment or by administration of a corresponding receptor antagonist (mecamylamine and naloxone, respectively). Neurosteroids were extracted from the cerebral cortex and plasma, fractionated by high-performance liquid chromatography, and quantitated by radioimmunoassay.
  
  
  RESULTS
  Acute intraperitoneal administration of nicotine (0.3-2 mg kg-1) or morphine (5-30 mg kg-1) induced dose- and time-dependent increases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, and allopregnanolone. The effects of both drugs were abolished by adrenalectomy-orchiectomy. Spontaneous or naloxone-precipitated morphine withdrawal and mecamylamine-precipitated (but not spontaneous) nicotine withdrawal also increased neurosteroid concentrations in the brain and plasma. A challenge dose of nicotine or morphine, administered 14 or 24 h after the last drug injection in chronic ally treated rats, failed to increase cerebrocortical neurosteroid concentrations.
  
  
  CONCLUSIONS
  Changes in neurosteroid concentrations mediated by activation of the HPA axis may both contribute to the early acquisition phase of nicotine or morphine addiction and serve to counteract the anxiety-like behavior associated with nicotine or morphine withdrawal. However, the evidence that nicotine withdrawal did not increase neurosteroids, unless precipitated by mecamylamine, suggests that the role of these neurosteroids in spontaneous nicotine withdrawal may not be clear.
authors.affiliation: Department of Experimental Biology, Center of Excellence for Neurobiology of Dependence, University of Cagliari, Cagliari, Italy. aconcas@unica.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Concas
authors.forename: Cristiana
authors.initials: C
authors.lastname: Sogliano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Porcu
authors.forename: Carla
authors.initials: C
authors.lastname: Marra
authors.forename: Andrea
authors.initials: A
authors.lastname: Brundu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Biggio
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011280:Pregnanolone / Q000096:biosynthesis / Q000097:blood; D011284:Pregnenolone / Q000096:biosynthesis / Q000097:blood; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009294:Narcotics; D018733:Nicotinic Antagonists; D009270:Naloxone; D011374:Progesterone; D008464:Mecamylamine; D009538:Nicotine; D011284:Pregnenolone; D009020:Morphine; D011280:Pregnanolone