Steroids, neuroactive steroids and neurosteroids in psychopathology

Dubrovsky, B.

doi:10.1016/j.pnpbp.2004.11.001

Cited by 220 publications

(149 citation statements)

References 292 publications

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“…For strengthened Sig-1R activity in the CCD pain state, the endogenous Sig-1R ligands should be increased and this will be accompanied with the increase of the receptor population. The possibility that neurosteroids could be endogenous activators/inactivators of Sig-1R and possibly be even the 'endogenous ligand' for this receptor has generated significant interest in this area [17]. Recent data has demonstrated that the production of neurosteroids such as estradiol and progesterone is up-regulated in DRG neurons after chronic nerve injury [18].…”

Section: Discussionmentioning

confidence: 99%

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

Son

Kwon

2010

Korean J Physiol Pharmacol

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Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. W hen stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0∼ 5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

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Section: Discussionmentioning

confidence: 99%

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

Son

Kwon

2010

Korean J Physiol Pharmacol

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“…Although the usefulness of DHEA as an antidepressant has been suggested (Dubrovsky, 2005;Wolf and Kirschbaum, 1999;Wolkowitz et al, 1999), its mechanism of action and role in depression is poorly understood. Herein, we used an animal model of depression (FSL rats) to demonstrate alterations in DHEA levels in some brain regions relevant to depression.…”

Section: Discussionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

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“…It would be renowned that according to preceding studies, stress stimulates HPA axis and upsurges secretion of epinephrine and glucocorticoids from the central and cortical parts of the adrenal gland, respectively (McEwen, 2007; B Hunter et al, 2010). It has been reported that the reduced level of dopamine in the nucleus accumbens recovers the animal's ability to acquire used to stress following inescapable stress (Dubrovsky, 2005;Viveros et al, 2007;Colomer and Olivos-Oré et al, 2010;Hunter and Bloss et al, 2010). Various parts of reward system are involved in the variation of stress responses and the nucleus accumbens as a main parts of this reward system, acting a vital role in inhibiting the effects of stress (Zhao et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Intra-accumbal and Peripheral administration of nicotine reduces the side-effects of Inescapable Stress

2017

J App Pharm Sci

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Background:The mesolimbic dopaminergic system plays an important role in controlling the effects of stress. Here, the role of nicotinic receptors in the nucleus accumbens, one of the most important parts of the mesolimbic system in reducing the effects of stress in mice has been studied. Methods:Bilateral intra-accumbal (shell of nucleus accumbens; sNA) cannulation was performed carefully. Animals were allocated randomly into nine groups and received nicotine intra-peritoneally (IP; 0.25, .05, and 1 ml/Kg) and intra-accumbally (sNA; 1, 5 and 10 μg/mouse), respectively. 30 minutes later saline and nicotine injection, the animal received an electric shock stress from the soles of the feet for 60 seconds. The body, brain and adrenal glands weight, food and water consumption and anorexia time were evaluated. Results:The results showed that IP administration of 1 mg/Kg nicotine (IP Nic 1) and intra-accumbal injection of 1 and 5 μg/mouse nicotine (NAc Nic 1 and 5) lead to weight loss. Although, intra-sNA injection of nicotine couldn't improve the food consumption, but the significant increases in food intake were observed in the IP Nic 1. The water intake increased and the brain weight decreased dose-dependently by rises of nicotine dose. The weight of the adrenal gland was significantly raised in IP Nic groups. Anorexia (decreased appetite), decreased or increased depending on the nicotine dose. Conclusion:We conclude that intra-accumbal nicotine administration reduces the signs of stress in a dose dependent manner, which probably is associated with the role of nicotinic acetylcholine receptors.

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Steroids, neuroactive steroids and neurosteroids in psychopathology

Cited by 220 publications

References 292 publications

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Intra-accumbal and Peripheral administration of nicotine reduces the side-effects of Inescapable Stress

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