Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia

Takashima, Koichiro; Kawasaki, Satoshi; Kimura, Shuichi; Fujita, Reiko; Sasaki, Kazuhiko

doi:10.1016/s0168-0102(02)00024-x

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…This suggests that progesterone may be an allosteric modulater of the β 2 *-nAChR and is consistent with preclinical literature suggesting that progesterone 54–56 and its Aring metabolites 55 inhibit nAChRs noncompetitively. Progesterone 57 and the neurosteroid pregnenolone 58 also have been shown to block nicotinic receptor function, and progesterone has reduces the urge to smoke 59, 60 . Taken together, these findings suggest that progesterone treatment for smoking cessation should be explored.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

Cosgrove

Esterlis²,

McKee³

et al. 2012

Arch Gen Psychiatry

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Context Sex differences exist in the reinforcing effects of nicotine, smoking cessation rates, and in response to nicotine replacement therapies. Sex differences in availability of nicotinic acetylcholine receptors containing the β2 subunit (β2*-nAChRs) may underlie differential nicotine and tobacco smoking effects and related behaviors in women and men. Objective To examine β2*-nAChR availability between male and female smokers and nonsmokers. To determine relationships between β2*-nAChR availability and tobacco smoking characteristics and female sex steroid hormones. Design Male (n=26) and female (n=28) tobacco smokers participated in one [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT) scan at 7–9 days of abstinence. Age-matched male (n=26) and female (n=30) nonsmokers participated in a single [123I]5-IA SPECT scan. All participants completed 1 magnetic resonance imaging study. Setting Academic Imaging Center Participants Tobacco smokers (n=54) and age- and sex-matched nonsmokers (n=56). Main Outcome Measure [123I]5-IA SPECT images were converted to equilibrium distribution volumes and analyzed using regions-of-interest. Results β2*-nAChR availability was significantly higher in male smokers compared to male nonsmokers in striatum, cortex and cerebellum, but female smokers did not have higher β2*-nAChR availability than female nonsmokers in any region. In women, β2*-nAChR availability in the cortex and cerebellum was negatively and significantly correlated with progesterone level on the day of the scan. In female smokers, on the day of the scan, progesterone levels were positively and significantly correlated with depressive symptoms, craving for a cigarette, and nicotine withdrawal. Conclusions The regulatory effects of nicotine in the brain, i.e., tobacco-smoking induced upregulation of β2*-nAChRs, appear to be distinctly different between men and women, and female sex hormones likely play a role in this regulation. These findings suggest an underlying neurochemical mechanism for the reported behavioral sex differences. In order to treat female smokers more effectively, it is critical that non-nicotinic mediated medications are explored.

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Section: Discussionmentioning

confidence: 99%

Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

Cosgrove

Esterlis²,

McKee³

et al. 2012

Arch Gen Psychiatry

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“…Progesterone (13)(14)(15) and its A-ring metabolites (14) noncompetitively inhibit nAChR. Progesterone (16) and the neurosteroid pregnenolone (17) also have been shown to block nicotinic receptor response. Conversely, estradiol has been shown to potentiate acetylcholine-evoked currents in human neuronal nAChRs by interacting at the a 4 subunit (18).…”

mentioning

confidence: 99%

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Cosgrove

Mitsis

Bois

et al. 2007

Journal of Nuclear Medicine

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The study of the effects of sex and hormones on brain chemistry and neurotransmission is of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. We examined the availability of nAChR containing the b 2 subunit in healthy men and women and the influence of menstrual phase among women. Methods: Ten men and 19 women nonsmokers underwent one 123 I-5-IA-85380 ( 123 I-5-IA) SPECT scan and one MRI scan. A subset of 9 women, aged 18-39 y, underwent a second 123 I-5-IA scan. These 9 women were scanned during the early follicular (days 4-7 in 8 subjects and day 11 in 1 subject) and mid-luteal (days 19-25) phases of their menstrual cycle. Hormone levels were measured in all women to confirm the phase of the cycle. Results: Regional brain activity (kBq/cm 3 ) was higher (39%-54%) in women than in men nonsmokers. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (V T 9), differences of 10%-16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (V T ), there was less than a 4% difference by sex in regional brain b 2 -nAChR availability. These sex differences in kBq/cm 3 and V T 9 resulted from significantly higher levels of total plasma parent, free fraction (f 1 ), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain b 2 -nAChR availability were observed across the menstrual cycle for any outcome measure. Conclusion: Overall, these findings demonstrate no significant difference in brain b 2 -nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate sex differences in radiotracer metabolism and plasma protein binding and highlight the critical need to measure plasma radiotracer levels and f 1 in studies that include both sexes. The importance of studying sex differences in brain neurochemistry has become increasingly evident with the recent demonstration of differences between men and women in symptomatology and treatment for many neuropsychiatric disorders. Evidence of differences in brain structure, function, neurotransmission, and receptor availability between men and women is mounting (1). Sex differences exist in a variety of behaviors related to tobacco smoking, such as craving, sensitivity to nicotine, and response to nicotine replacement therapy (2,3); however, the mechanisms underlying these differences are unclear. Women often experience more difficulty in quitting smoking than men (4-9), and rates of success may differ by menstrual phase. For example, women who quit smoking during the luteal phase of the menstrual cycl...

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“…This suggests that nicotinic acetylcholine receptor might be affected by progesterone. Other in vitro studies (Kudo, Tachikawa, & Kashimoto, 2002; Takashima, Kawasaki, Kimura, Fujita, & Sasaki, 2002) of adrenal chromaffin cells have also shown that progesterone interferes with nicotinic receptors. These findings suggest that pregnenolone sulfate (progesterone metabolite) inhibits nicotinic receptor-operated ion channels and may modulate nicotinic receptor-mediated responses in the brain.…”

Section: Discussionmentioning

confidence: 90%

“…This suggests that nicotinic acetylcholine receptor might be affected by progesterone. Other in vitro studies (Kudo, Tachikawa, & Kashimoto, 2002;Takashima, Kawasaki, Kimura, Fujita, & Sasaki, 2002) of adrenal chromaffin cells have also shown that This document is copyrighted by the American Psychological Association or one of its allied publishers.…”

Section: Discussionmentioning

confidence: 95%

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

Allen¹,

Petersen²,

Harrison³

et al. 2020

Experimental and Clinical Psychopharmacology

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Preclinical and clinical literature suggest that sex hormones impact tobacco use behaviors in women. The goal of this double-blind crossover laboratory study was to examine the effect of oral exogenous progesterone (200 mg twice per day) versus placebo on nicotine response using measures of motor speed and cognitive function in women following overnight smoking abstinence. We hypothesized that increased progesterone would blunt the nicotine response whereby producing less change in motor speed and cognition in response to nicotine exposure. Female smokers, age 18–35, were randomized to participate in two 9-day crossover testing weeks. Participants completed a lab session following overnight abstinence where they were administered nicotine nasal spray and asked to complete measures of immediate memory (IMT), delayed memory (DMT), word recall (WR), and finger tapping speed (FT). After the first 9-day testing week, participants resumed smoking and returned the following month to complete the identical lab session in the crossover condition. Forty-seven women were included in this analysis (n = 47). We found no differences in the magnitude of response for IMT, DMT, and WR between conditions. For FT, women had a blunted response to nicotine during the placebo condition. When examining the association between hormone levels and relative performance, we found increases in DMT, WR, and FT but decreases in IMT during the progesterone condition. We observed differences between progesterone versus placebo in relative change in some measures of nicotine response following overnight abstinence. Future studies are needed to further characterize this response.

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Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia

Cited by 5 publications

References 30 publications

Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

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Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia

Cited by 5 publications

References 30 publications

Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

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Resources

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Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers

Sex Differences in Availability of β₂*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers