Stress-induced increase in brain neuroactive steroids: Antagonism by abecarnil

Barbaccia, Maria Luisa; Roscetti, Gianna; Bolacchi, Francesca; Concas, Alessandra; Mostallino, Maria Cristina; Purdy, Robert H.; Biggio, Giovanni

doi:10.1016/0091-3057(95)02133-7

Cited by 99 publications

(53 citation statements)

References 28 publications

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“…In this study, as L-TP infusion was started randomly during the cycle, the luteal phase concentrations of allopregnanolone and other measured neuroactive steroids cannot be considered to be basal values as, on retrospective analysis, these women had already received L-TP infusion on at least three prior occasions, and two reported symptom improvement in the luteal phase of the challenge month. Alternatively, women with PMS may have been more stressed than controls, and allopregnanolone is known to increase after stress (15,16). Higher levels of perceived stress and physiological arousal in women with PMS has been shown in response to activities of daily living and experimental stress paradigms (34±36).…”

Section: Discussionmentioning

confidence: 99%

Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Rasgon

Serra²,

Biggio³

et al. 2001

European Journal of Endocrinology

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Objective: To evaluate the circulating concentrations of the neuroactive steroids in response to an i.v. L-tryptophan (L-TP) challenge across the menstrual cycle in women with premenstrual syndrome (PMS) and in controls. Method: An i.v. L-TP challenge was administered eight times during 1 month to five women with prospectively documented PMS and five age-and body mass-matched controls. Progesterone, allopregnanolone pregnenolone and 3a-5a-tetrahydrocorticosterone were assessed 15 and 0 min before, and at 30, 60 and 90 min after the challenge, across the menstrual cycle. Results: In response to L-TP challenge, only allopregnanolone concentrations were significantly increased across the cycle and this increase was of a greater magnitude in women with PMS. Pregnenolone and 3a-5a-tetrahydrocorticosterone concentrations were not affected in women with PMS or controls after L-TP challenge. Conclusions: The data provide evidence for possible interaction between the serotonergic system and the neuroactive steroid, allopregnanolone. Women with PMS demonstrated a more significant increase in allopregnanolone concentrations in response to L-TP challenge, which could be due to an initial low basal serotonergic tone in the luteal phase in the PMS group.

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Section: Discussionmentioning

confidence: 99%

Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Rasgon

Serra²,

Biggio³

et al. 2001

European Journal of Endocrinology

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“…Notably, E 2 increases 3α,5α-THP in the hippocampus [8,9,21], which is an important area for affective processes [17]. Further, stressful or challenging environmental experiences increase biosynthesis of E 2 and 3α,5α-THP [22][23][24][25]. As such, we were interested in the effects of E 2 and/or 3α,5α-THP on behaviors that may promote sexual interactions (exploration, anxiety, social behaviors) and whether actions of E 2 and/or 3α,5α-THP in the VTA are sufficient to modulates these behaviors.…”

Section: Introductionmentioning

confidence: 99%

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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Abstract17β-Estradiol (E 2 ) and progesterone (P 4 ) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P 4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), modulates lordosis of E 2 -primed rodents; 3α,5α-THP can also influence anxiety and social behaviors. To examine if 3α,5α-THP in the VTA mediates socio-sexual behaviors, we infused 3α,5α-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E 2 , P 4 , dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3α,5α-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3α,5α-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3α,5α-THP, but neither E 2 nor P 4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3α,5α-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

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“…The highest concentrations of pregnenolone and pregnenolone sulfate in the central nervous system are less than 1 μM (Corpechot et al, 1983;Lanthier and Patwardhan, 1986), the concentration at which neuromodulation is observed. It is possible that these neuromodulatory concentrations are obtained locally at sites of pregnenolone sulfate synthesis (Compagnone et al, 1995a;Hu et al, 1987;Jung-Testas et al, 1989), and may be increased, for example, after stress (Barbaccia et al, 1996;Purdy et al, 1991). P450scc, the enzyme that converts cholesterol into pregnenolone, is found in rodent brains early in development (Compagnone et al, 1995a;Hammer et al, 2004).…”

Section: Action At Ligand-gated Ion-channel Receptorsmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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Stress-induced increase in brain neuroactive steroids: Antagonism by abecarnil

Cited by 99 publications

References 28 publications

Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Neuroactive steroid-serotonergic interaction: responses to an intravenous L-tryptophan challenge in women with premenstrual syndrome

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Neurosteroid regulation of central nervous system development

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