Allopregnanolone has no effect on startle response and prepulse inhibition of startle response in patients with premenstrual dysphoric disorder or healthy controls.
BACKGROUND
Allopregnanolone is an endogenous neuroactive steroid which, through the binding to the GABA(A) receptor, enhances inhibitory neurotransmission and exerts anxiolytic, sedative and antiepileptic effects. Following acute administration, allopregnanolone reliably acts as an anxiolytic compound. The primary aim of this study was to investigate if allopregnanolone, administered to healthy women and women with premenstrual dysphoric disorder (PMDD), would have an anxiolytic effect, expressed as a decreased startle response.


METHODS
Sixteen PMDD patients and twelve healthy controls completed the study. The participants were scheduled for the startle tests twice in the luteal phase. During the test sessions an intravenous allopregnanolone and placebo bolus injection was administered in double-blinded, randomized order at intervals of 48 h. Following the allopregnanolone/placebo injections startle response and prepulse inhibition of startle response (PPI) were assessed by electromyography.


RESULTS
Following the intravenous allopregnanolone administration the serum concentrations of allopregnanolone increased to 50-70 nmol/l, corresponding to levels that are seen during pregnancy. The obtained serum concentrations of allopregnanolone were significantly lower in PMDD patients than among the healthy controls, p<0.05. The allopregnanolone injection resulted in significant increases of self-rated sedation in both groups, p<0.01. Allopregnanolone did not induce any changes in startle response or prepulse inhibition of startle response in comparison to placebo. No differences in allopregnanolone-induced changes in startle response or PPI could be detected between PMDD patients and controls subjects.


CONCLUSIONS
Startle response and PPI were unaffected by acute intravenous administration of allopregnanolone in PMDD patients and healthy controls.
Kask
Kristiina
K
Department Women's and Children's Health, Uppsala University, Uppsala, Sweden. Kristiina.kask@kbh.uu.se
Bäckström
Torbjörn
T
Lundgren
Per
P
Sundström Poromaa
Inger
I
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D011280:Pregnanolone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011293:Premenstrual Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D011963:Receptors, GABA-A / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects*; D055815:Young Adult
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D011280:Pregnanolone