title: Influence of acute or chronic administration of ovarian hormones on the effects of desipramine in the forced swim test in female rats.
abstract: BACKGROUND
  Gender may influence antidepressant (AD) treatment outcome. In order to address this preclinically, the potential effects of ovarian hormones on AD treatment in ovariectomized female rats were investigated.
  
  
  OBJECTIVE
  In the first study, the effect of acute administration of estrogen and progesterone on the antidepressant-like effects of desipramine (DMI), a selective norepinephrine reuptake inhibitor (SNRI), was investigated in the forced swimming test (FST). In the second study, the effect of chronic administration of these hormones on the effects of chronically administered DMI was investigated.
  
  
  RESULTS
  In the acute study, the hormones blocked the effects of DMI in the FST as demonstrated by the absence of either a reduction in immobility or an increase in climbing behavior in animals treated with DMI in combination with the hormones. Concentration-response experiments on hippocampal synaptosomes revealed no changes in the Km or Bmax for uptake of (3)H-NE in hormone-treated rats. In the chronic study, the antidepressant-like effects of DMI in the FST were not blocked by chronic administration of hormones. Interestingly, the hormones affected the serum concentrations of DMI. These levels were significantly higher in animals receiving 10 or 15 mg/kg/day in hormone-treated rats as compared to those with placebo.
  
  
  CONCLUSIONS
  Acute administration of hormones blocked the effects of DMI (given three times over 24 h) in the FST. However, chronic administration of these hormones failed to block the effects of chronically administered DMI (at a dose that produces clinically relevant serum concentrations).
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229-3900, USA, shahap@uthscsa.edu.
authors.forename: Aparna
authors.initials: A
authors.lastname: Shah
authors.forename: Alan
authors.initials: A
authors.lastname: Frazer
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D003891:Desipramine