The Role of Sigma Receptors in Depression

Bermack, Jordanna E.; Debonnel, Guy

doi:10.1254/jphs.crj04005x

Cited by 121 publications

(102 citation statements)

References 195 publications

(130 reference statements)

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…A number of authors have discussed the importance of the glutamate system, e.g., [15][16][17][18] , and its regulation 19,20 . The following discussion not only addresses, glutamate, GABA, and glycine but also details how excitatory amino acids may interact with the glutamate system.…”

Section: The Glutamate Systemmentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

View full text Add to dashboard Cite

Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

show abstract

Section: The Glutamate Systemmentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…Among the SSRIs, fluvoxamine was the most potent (K i ¼ 36 nM) for sigma-1 receptors, and paroxetine was weak (K i ¼ 1893 nM) for sigma-1 receptors, suggesting that these receptors may in some way play a role in the mechanisms of action of fluvoxamine (Narita et al, 1996;Hashimoto and Ishiwata, 2006). Multiple lines of evidence suggest that sigma-1 receptors play a role in the pathophysiology of neuropsychiatric diseases such as schizophrenia, anxiety disorders, and depression, as well as in the evolution of cognitive deficits associated with these conditions (Debonnel and de Montigny, 1996;Maurice et al, 2001;Su and Hayashi, 2003;Hayashi and Su, 2004;Takebayashi et al, 2004;Bermack and Debonnel, 2005;Hashimoto and Ishiwata, 2006).…”

Section: Introductionmentioning

confidence: 99%

Phencyclidine-Induced Cognitive Deficits in Mice are Improved by Subsequent Subchronic Administration of Fluvoxamine: Role of Sigma-1 Receptors

Hashimoto

Fujita

Iyo

2006

Neuropsychopharmacol

122

101

View full text Add to dashboard Cite

This study was undertaken to examine the effects of the selective serotonin reuptake inhibitors fluvoxamine and paroxetine on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). In the novel object recognition test, repeated administration of PCP (10 mg/kg/day, 10 days) significantly decreased the exploratory preference in the retention test session, but not in the training test session. PCP-induced cognitive deficits were significantly improved by subsequent subchronic (2-week) administration of fluvoxamine (20 mg/kg/day), but not paroxetine (10 mg/kg/day). Furthermore, the effect of fluvoxamine on PCP-induced cognitive deficits was antagonized by co-administration of the selective sigma-1 receptor antagonist NE-100 (1 mg/kg/day). Moreover, PCP-induced cognitive deficits were also significantly improved by subsequent subchronic (2-week) administration of the selective sigma-1 receptor agonist SA4503 (1 mg/kg/day) or neurosteroid dehydroepiandrosterone 3-sulfate (DHEA-S; 25 mg/kg/day). The effects of SA4503 or DHEA-S were also antagonized by co-administration of NE-100 (1 mg/kg/day), suggesting the role of sigma-1 receptors in the active mechanisms of these drugs. In contrast, acute single administration of these drugs (fluvoxamine, paroxetine, SA4503) alone or combination with NE-100 did not alter PCP-induced cognitive deficits. The present study suggests that agonistic activity of fluvoxamine at sigma-1 receptors plays a role in the active mechanisms of fluvoxamine on PCP-induced cognitive deficits in mice. Therefore, sigma-1 receptor agonists such as fluvoxamine would be potential therapeutic drugs for the treatment of the cognitive deficits of schizophrenia.

show abstract

“…Ishima and colleagues (Ishima et al 2008) showed that both sigma 1 receptors and IP 3 receptors are involved in the potentiation of NGFinduced neurite outgrowth by acetylcholinesterase inhibitor donepezil, which is known to bind to sigma 1 receptors in the brain. Accumulating evidence suggests that sigma 1 receptors are involved in both neuroplasticity and pathophysiology of neuropsychiatric diseases such as major depressive disorders, anxiety, schizophrenia and Alzheimer's disease Takebayashi et al 2004;Bermack and Debonnel 2005). Sigma 1 receptors form a trimeric complex with two other proteins on the endoplasmic reticulum: IP 3 receptor and the ankyrin isomer 220.…”

Section: Discussionmentioning

confidence: 99%

Haloperidol increases expression of the inositol 1,4,5-trisphosphate receptors in rat cardiac atria, but not in ventricles

Novàkovâ

Sedláková²,

Sirova³

et al. 2010

gpb

View full text Add to dashboard Cite

Abstract. Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias. High affinity binding sites for the prototypical sigma ligand haloperidol were found in membranes of cardiac myocytes from adult rats. Activation of sigma 1 receptor leads to a release of calcium from the endoplasmic reticulum that follows increased synthesis of inositol 1,4,5-trisphosphate (IP 3 ).We studied the effect of long-term haloperidol treatment on the expression of sigma 1 receptors, IP 3 receptors of type 1 and 2 in the individual parts of the rat heart, in isolated rat cardiomyocytes and in PC12 cells.We have found that prolonged treatment with haloperidol significantly increased mRNA levels of sigma 1 receptors in both atria and ventricles. Sigma 1 receptor's mRNA was increased also in isolated cardiomyocytes. Haloperidol treatment affects the expression of IP 3 receptors of type 1 and 2 in cardiac atria, but not in cardiac ventricles. We observed increase in IP 3 receptors in differentiated PC12 cells, but not in isolated cardiomyocytes. We propose that this increase might participate in triggering cardiac arrhythmias during haloperidol treatment, which has to be further verified.

show abstract

The Role of Sigma Receptors in Depression

Cited by 121 publications

References 195 publications

A Review of Glutamate Receptors I: Current Understanding of Their Biology

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Phencyclidine-Induced Cognitive Deficits in Mice are Improved by Subsequent Subchronic Administration of Fluvoxamine: Role of Sigma-1 Receptors

Haloperidol increases expression of the inositol 1,4,5-trisphosphate receptors in rat cardiac atria, but not in ventricles

Contact Info

Product

Resources

About