Acute effects of triazolam in women: relationships with progesterone, estradiol and allopregnanolone.
This study investigated hormone levels and mood in normal women to explore relationships between levels of circulating hormones and i) baseline mood states and ii) effects of triazolam on mood. Certain ovarian hormones or their metabolites have direct actions on neuronal receptors. These actions may result in changes in mood state, or changes in responses to psychoactive drugs which act on the same receptors. The present study explored relationships between estrogen, progesterone and a metabolite of progesterone, allopregnanolone, and the mood-altering and performance effects of an acute dose of triazolam. Triazolam is a short-acting benzodiazepine which acts via the GABAA receptor complex. Twenty women received triazolam (0.25 mg) or placebo at the follicular, ovulatory and luteal phases of their menstrual cycle. Each subject participated in six conditions (i.e., drug and placebo at each of the three phases), across two menstrual cycles. Dependent measures included self-reported mood states, psychomotor performance, and plasma levels of estradiol, progesterone, allopregnanolone, and triazolam. Mood and performance measures were not clearly related to hormone levels when data from all three phases were examined. However, within the luteal phase, higher levels of allopregnanolone were associated with lower self-reported arousal before any drug administration (i.e., at baseline). After administration of triazolam, most subjects reported the expected decreases in rating of arousal. However, the subjects with the highest levels of allopregnanolone reported increases in ratings of arousal. Thus, hormone levels were related to mood and responses to triazolam, particularly during the luteal phase of the cycle. However, the drug-hormone interactions on mood and behavior were complex.
de Wit
H
H
Department of Psychiatry, University of Chicago, IL 60637, USA.
Rukstalis
M
M
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011280:Pregnanolone / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D013997:Time Factors; D014229:Triazolam / Q000494:pharmacology*
D018696:Neuroprotective Agents; D014229:Triazolam; D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone