Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to ?1 receptors in the mouse forebrain

Maurice, Tangui; Roman, François J.; Privat, Alain

doi:10.1002/(sici)1097-4547(19961215)46:6<734::aid-jnr10>3.0.co;2-u

Cited by 92 publications

(39 citation statements)

References 33 publications

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“…In the present study, PROG at 10-50 mg/kg, which inhibit the in vivo haloperidol-sensitive [ 3 H]-(ϩ)-SKF-10,047 binding to sigma 1 receptor in the mouse hippocampus and cortex (Maurice et al 1996), had no effect on the conditioned fear stress response in mice. Like NE-100, PROG be- NEUROPSYCHOPHARMACOLOGY 2000-VOL.…”

Section: Discussionsupporting

confidence: 66%

Section: Receptor Agonist ( ϩ )-N-allylnormetazocine (( ϩ )-contrasting

confidence: 48%

“…Several steroids including PROG, PREG, PREGS, testosterone, (Klein and Musacchio 1994;McCann and Su 1991;Ross 1991;Schwartz et al 1989;Su et al 1988;Yamada et al 1994). DHEAS and PREGS dosedependently inhibited the in vivo haloperidol-sensitive [ 3 H]-(ϩ)-SKF-10,047 binding to sigma 1 receptor in the mouse hippocampus and cortex (Maurice et al 1996). Taken together, these findings suggest that the attenuating effects of neurosteroids on the conditioned fear stress are mediated at least partly through the sigma 1 receptors.…”

mentioning

confidence: 99%

“…Some neurosteroids such as PREGS and PROG have been shown to have an affinity for sigma 1 receptors (Su et al 1988;Walker et al 1990). Further, Maurice et al (1996) have reported that exogenous administration of neurosteroids leads to dose-dependent inhibition of in vivo binding of [ -10,047) to sigma 1 receptors. Thus, it is possible that neurosteroids are the main endogenous modulator of sigma 1 receptors, and that the pharmacological effects of neurosteroids described above are mediated, at least partly, through the sigma 1 receptors.…”

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confidence: 99%

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Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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Mice exhibited a marked suppression of motility (conditioned fear stress) when placed in an environment in which they had previously received an electric footshock. This conditioned fear stress response was dose-dependently attenuated by neurosteroids such as dehydroepiandrosterone sulfate (DHEAS; 25 and 50 mg/kg, s.c.) and pregnenolone sulfate (PREGS; s.c.), and by a putative sigma 1 047; 3 and 6 mg/kg, s.c.). However, progesterone (PROG; s.c.) and allopregnanolone (5 and 20 mg/kg, s.c.) had no effect on this stress response. The attenuating effects of DHEAS (50 mg/kg, s.c.), PREGS (50 mg/kg, s.c.), and ( ϩ )- 047 (6 mg/kg, s.c.) were reversed by i.p.), a sigma 1 receptor antagonist and PROG (5 or 10 mg/kg, i.p.). When DHEAS (25 mg/kg) was co-administered with ( ϩ )- 047 (3 mg/kg) Neurosteroids are synthesized in the brain, either de novo from cholesterol or from steroid hormone precursors, and accumulate in the nervous system to levels that are at least in part independent of steroidogenic gland secretion (Baulieu 1981). Neurosteroids, such as progesterone (PROG), pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their respective sulfate ester (PREGS or DHEAS), are involved in regulating the imbalance between excitation and inhibition in the CNS (Wu et al. 1991). The neurosteroids, allopregnanolone, allotetrahydrodeoxycorticosterone, PREGS, and DHEAS have been shown to possess antistress, anxiolytic, and antiamnesic properties in experimental animal models (Bitran et al. 1991;Brot et al. 1997;Maurice et al. , 1999Urani et al. 1998;Wieland et al. 1991). Recent evidence suggests that DHEAS and PREGS also play an important role in depression. Interestingly, decreased levels of DHEA, DHEAS, and PREGS have been associated with depression, cognitive dysfunction, aging, and other neurological conditions (Orentreich et al. 1984;Vallée et al. 1997), and DHEA improves the depression score in patients (Wolkowitz et al. 1997). However, the From the Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine (YN, HK, YK, TN, TN), Nagoya, Japan; and Department of Clinical Pharmacy, Faculty of Pharmacy, Meijo University (YK, TN, MN), Nagoya, Japan. receptor agonist, ( ϩ )-N-allylnormetazocine (( ϩ )-Address correspondence to: Dr. Toshitaka Nabeshima, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.Received October 18, 1999; revised February 2, 2000; accepted February 18, 2000. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 3 Neurosteroids and Sigma 1 Receptors 277 mechanism underlying the beneficial effects of neurosteroids is not yet known.Neurosteroids have been shown to affect the activity of neurotransmitter systems, which are involved in a variety of neuropsychiatric illnesses. DHEAS and PREGS are negative allosteric modulators of the ␥ -aminobutyric acid (GABA) A receptors (Majewska 1992), and positive modulators of N-methyl-D-aspartate (NMDA) receptor-mediated res...

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Section: Discussionsupporting

confidence: 66%

Section: Receptor Agonist ( ϩ )-N-allylnormetazocine (( ϩ )-contrasting

confidence: 48%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Noda

Kamei

et al. 2000

Neuropsychopharmacology

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“…Su and collaborators (1988) showed an inhibition of [ 3 H](+)-SKF 10,047 binding in the guinea-pig brain and of [ 3 H]-haloperidol in the spleen by progesterone with Ki values in the nanomolar range. Other steroids, such as testosterone, pregnenolone sulfate, or deoxycorticosterone, exhibit Ki values in the micromolar range (McCann and Su 1991;Maurice et al 1996). Confirming these studies, other groups have shown that progesterone was indeed the neurosteroid which most potently inhibited the binding of 3 Poncelet et al (1993) several sigma-1 ligands in different preparations, such as the rat brain, splenocytes plasma membrane, and liver microsomes (Ross 1991;Klein and Musacchio 1994;Yamada et al 1994).…”

Section: Endogenous Ligands Of the Sigma Receptorsmentioning

confidence: 89%

Sigma receptors: biology and therapeutic potential

Guitart¹,

Codony²,

Monroy³

2004

Psychopharmacology

221

230

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More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

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Neuroprotective and Neurogenic Properties of Dehydroepiandrosterone and its Synthetic Analogs

Charalampopoulos

Lazaridis

Gravanis

2011

Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis

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Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate ester (DHEAS) are the most abundant steroids in humans. They are mainly produced by the zona reticularis of the adrenal cortex. In the early 1980s, both steroids were shown to be also produced within the nervous system [1, 2]. The enzymes required for the synthesis of DHEA were found to be expressed in neurons, astrocytes, and oligodendrocytes. The first step for the biosynthesis of DHEA is cholesterol's side chain cleavage by cytochrome P450scc and the production of pregnenolone, which is then metabolized to DHEA by the 17α-hydroxylase/c17 and 20-lyase activities of cytochrome P450c17. DHEA can be bidirectionally converted to the sulfated derivative DHEAS by hydroxysteroid sulfotransferase and back to DHEA by a sulfatase [3, 4]. During the development stages in mice, expression of P450c17 starts as early as E10.5 in neural crest cells and shortly after it is present in most of the spinal cord neural crest-derived tissues, including the peripheral nervous system (PNS) [5]. In the rat brain, cytochrome P450c17 is expressed during neonatal development and adulthood. The mRNA of P450c17 was found in the mesencephalon, cerebrum, diencephalon, and cerebellum with the expression levels being higher in the mesencephalon. High levels of P450c17 in association with lower levels of 3β-hydroxysteroid dehydrogenase/ 5 -4 -isomerase (3β-HSD), the enzyme that transforms DHEA to androstenedione, in the mesencephalon suggest that only DHEA -and not the other metabolites -is the main neurosteroid in this area [6]. Furthermore, P450c17 has been identified in hypothalamic and cortical neurons and astrocytes in culture [7, 8], as well as in neurons, astrocytes, and oligodendrocytes of the spinal cord of adult rats [9]. It is noteworthy that P450c17 is localized in the endoplasmic reticulum of the presynaptic and postsynaptic regions of pyramidal neurons in the hippocampal regions CA1-CA3, and in the granule neurons of the dentate gyrus, suggesting fast neuromodulatory actions of DHEA at the level of the synapse [10,11]. The presence of P450c17 has been also described in neuronal and glial cells of the brain and pituitary of frog [12]. The importance of DHEA for neuronal function is supported by experimental Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis.

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Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10,047 binding to ?1 receptors in the mouse forebrain

Cited by 92 publications

References 33 publications

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Neurosteroids Ameliorate Conditioned Fear Stress An Association with Sigma1 Receptors

Sigma receptors: biology and therapeutic potential

Neuroprotective and Neurogenic Properties of Dehydroepiandrosterone and its Synthetic Analogs

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