Background: Allopregnanolone (ALLO) is a neuroactive steroid metabolized from
progesterone and, therefore, varies by menstrual phase in premenopausal
women. Previously published literature has shown that risk for relapse to
smoking varies by menstrual phase. Further, recent preclinical research
indicates that ALLO may protect against drug abuse behaviors. Therefore, this
dissertation project aims to characterize ALLO by menstrual phase in women
with and without depressive symptoms (Paper #1) and explore the effect of ALLO
on smoking-related symptomatology (SRS; Paper #2) and nicotine response
(NR; Paper #3) during short-term smoking abstinence.
Methods: At screening, participants (n=87) were stratified by depressive
symptoms status and, using a controlled cross-over study design, were
randomized to testing order (i.e., follicular (F) menstrual phase followed by the
luteal (L) phase or vice versa (L-F)). The six-day testing week consisted of two
days of ad libitum smoking followed by four days of biochemically verified
smoking abstinence. ALLO was measured twice during each testing week:
during ad libitum smoking and on the fourth day of smoking abstinence.
Participants completed daily forms to assess SRS during the testing week. On
the fourth day of smoking abstinence, participants participated in a NR lab
session. Growth curve and covariance pattern models, adjusted for menstrual
phase and testing order, were used to assess the effect of ALLO on SRS and
Results: In the first paper (n=84), a significant menstrual phase difference was
observed in the change in ALLO level during smoking cessation. Specifically,
ALLO decreased by 10% in the F phase and increased by 31% in the L phase
(p<0.01). There were no significant differences in ALLO levels between the
depressive symptoms groups. In the second paper (n=64), the absolute level of ALLO on the day before quit was significantly associated with the following: (1)
perceived stress on the day before quit (β=-2.25, p<0.01), (2) the change in
perceived stress during smoking abstinence (β=0.79, p<0.01), and (3)
premenstrual symptoms of pain and water retention on the day before quit
(β=1.09, p<0.01; β=1.08, p<0.01; respectively). The change in ALLO during
smoking abstinence was significantly associated with the following: (1) positive
and negative affect on the day before quit (β=1.15, p<0.01; β=1.04, p=0.04;
respectively), (2) perceived stress on the day before quit (β=-1.77, p=0.01), (3)
the change in perceived stress during smoking cessation (β=0.17, p<0.01), and
(4) the change in depressive symptoms on the day of quit (β=-1.52, p=0.02).
Finally, in the third paper (n=77), ALLO had a significant, positive association
with the following variables prior to initiation of nicotine nasal spray: systolic
blood pressure (β=0.85, p=0.04), diastolic blood pressure (β=1.19, p<0.01), and
subjective levels of physical symptoms (β=0.58, p<0.01), dizziness (β =0.88,
p<0.01), jitteriness (β=0.90, p=0.04) and pleasantness (β=2.05, p=0.041). ALLO
also had significant associations with changes in cognition from baseline to post
nicotine nasal spray use: specifically, discriminability (a measure of attention;
β=1.15, p=0.05), and bias (a measure of impulsivity; β=0.12, p=0.02). Conclusion: ALLO varied significantly by menstrual phase and smoking status,
and had a significant effect on several measures of SRS and NR. While several
of these associations were favorable (i.e., perceived stress on the day before quit
and pleasantness on the fourth day of smoking abstinence), some were not (i.e.,
premenstrual symptoms on the day before quit and increased subjective report of
physical symptoms on the fourth day of smoking abstinence). Therefore, it
remains unknown whether or not ALLO is a protective factor against drug abuse
behaviors. Additional research is needed to explore the role of ALLO directly on
smoking cessation outcomes.
University of Minnesota Ph.D. dissertation. November 2012. Major: Epidemiology. Advisor: Harry Lando, PhD. 1 computer file (PDF); vii, 73 pages.
Allen, Alicia Marie.
Allopregnanolone during short-term smoking abstinence: associations with depressive symptoms, smoking-related symptomatology and nicotine response.
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