title: Physiological doses of progesterone potentiate the effects of triazolam in healthy, premenopausal women.
abstract: BACKGROUND
  Gender plays a critical role in the effects of drugs and drug abuse liability. Biological factors, including ovarian hormones, may contribute to gender differences in drug abuse. Preclinical and some clinical research suggests that progesterone and its metabolites have activity at the GABA(A) receptor and may enhance the effect of GABAergic compounds (e.g., benzodiazepines). Because women are exposed to varying levels of progesterone from puberty until menopause, and appear more sensitive to the negative consequences of benzodiazepine use, it is important to understand the impact of progesterone on GABAergic drug effects.
  
  
  OBJECTIVE
  The purpose of this experiment was to characterize the behavioral effects of progesterone, alone and in combination with the short-acting benzodiazepine, triazolam, to determine if progesterone potentiates the behavioral effects of triazolam.
  
  
  METHODS
  Oral micronized progesterone (0, 100, and 200 mg) and oral triazolam (0.00, 0.12, and 0.25 mg/70 kg) were administered to healthy, premenopausal women (n = 11) under conditions of low circulating sex hormones. The subjective, performance and physiological effects of progesterone, alone and in combination with triazolam, were assessed.
  
  
  RESULTS
  Triazolam alone produced prototypical sedative-like effects. Progesterone alone also engendered some sedative effects, although the time course of the effects was more limited than that of triazolam. Progesterone increased and extended the duration of triazolam effects and delayed the onset of triazolam peak effects, most notably at the 0.12 mg/70 kg dose.
  
  
  CONCLUSIONS
  Progesterone potentiates the behavioral effects of benzodiazepines and may contribute to benzodiazepine use and abuse among women.
authors.affiliation: Department of Behavioral Science, College of Medicine, University of Kentucky Medical Center, Lexington, KY 40536-0086, USA. babalonis@uky.edu
authors.forename: Shanna
authors.initials: S
authors.lastname: Babalonis
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Martin
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kelly
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014229:Triazolam / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018757:GABA Modulators; D011372:Progestins; D011963:Receptors, GABA-A; D014229:Triazolam; D011374:Progesterone