Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus

Naylor, Peter; Stewart, Caroline A.; Wright, Simon; Pearson, R.C.A.; Reid, Ian

doi:10.1016/0169-328x(95)00264-s

Cited by 45 publications

(21 citation statements)

References 26 publications

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“…Similar to our findings with lithium, it has been reported that monamine-acting antidepressants increase membrane levels of AMPA receptors (Martinez-Turrillas et al, 2005;Martinez-Turrillas et al, 2002). Electroconvulsive shock, an animal model of electroconvulsive therapy, was shown to increase the levels of GluR1 mRNA in the rat hippocampus (Naylor et al, 1996). It is unclear what the mechanism is by which modulation of AMPA receptors may be involved in the mechanism of antidepressant action, or to what extent AMPA activation is required for therapeutic action in humans (Bleakman et al, 2007).…”

Section: Discussionsupporting

confidence: 84%

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

et al. 2008

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In addition to its clinical antimanic effects, lithium also has efficacy in the treatment of depression. However, the mechanism by which lithium exerts its antidepressant effects is unclear. Our objective was to further characterize the effects of peripheral and central administration of lithium in mouse models of antidepressant efficacy as well as to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in these behaviors. We utilized the mouse forced swim test (FST) and tail suspension test (TST), intracerebroventricular (ICV) lithium administration, AMPA receptor inhibitors, and BS3 crosslinking followed by western blot. Both short-and long-term administration of lithium resulted in robust antidepressant-like effects in the mouse FST and TST. Using ICV administration of lithium, we show that these effects are due to actions of lithium on the brain, rather than to peripheral effects of the drug. Both ICV and rodent chow (0.4% LiCl) administration paradigms resulted in brain lithium concentrations within the human therapeutic range. The effects of lithium to decrease immobility in the FST and TST were blocked by administration of AMPA receptor inhibitors. Additionally, administration of lithium increased the cell surface expression of GluR1 and GluR2 in the mouse hippocampus. Collectively, these data show that lithium exerts centrally mediated antidepressant-like effects in the mouse FST and TST that require AMPA receptor activation. Lithium may exert its antidepressant effects in humans through AMPA receptors, thus further supporting a role of targeting AMPA receptors as a therapeutic approach for the treatment of depression. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Depression is a severe neuropsychiatric disorder that manifests both as a component of bipolar disorder and unipolar depressive disorder. Bipolar disorder affects at least 1% of the world's population when a strict definition (DSM IV bipolar I disorder) is applied. Major depression is more common than bipolar disorder in the overall population (~ 15% lifetime risk as defined by DSM IV) (Kessler et al., 2005;Sullivan et al., 2000). The recognition of the significant morbidity and mortality (suicide rate of 15%) associated with these severe mood disorders (Evans et al., 2005;Jamison, 2000;Kupfer, 2005), as well as the growing appreciation that a significant percentage of patients either do not respond fully to existing treatments or are intolerant of undesirable side effects, has made the challenge of discovering improved therapeutic agents increasing...

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Section: Discussionsupporting

confidence: 84%

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

et al. 2008

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“…16,17 A series of spaced ECS treatments was also shown to enhance the expression of Narp protein, an immediate early gene product that probably plays a regulatory role in the clustering of AMPA receptors at synaptic sites. 30 Although the expression of mRNA for the NR1 subunit was unchanged in our study, 28 ECS treatment has been shown to alter the expression of mRNA for other NMDA receptor subunits. Watkins et al 31 found that chronic ECS treatment produced an acute increase in mRNA for both the NR2A and NR2B subunits of the NMDA receptor in the dentate gyrus, although only the NR2B increase was sustained 24 h later.…”

Section: Molecular Mechanisms Underlying the Ecs Effectcontrasting

confidence: 57%

“…Expression of mRNA for the NR1A-G subunit was unchanged relative to anaesthetised controls. 28 Wong et al 29 also found an increase in GluR1 expression following ECS treatment. This increase in mRNA levels is suggestive of an up-regulation in postsynaptic AMPA receptors that may be responsible for the long-lasting electrophysiological changes seen in the dentate gyrus.…”

Section: Molecular Mechanisms Underlying the Ecs Effectmentioning

confidence: 92%

“…This is consistent with the effects of ECS treatment on the NR1 subunit described above. 28 However, mRNA for the mouse epsilon 1 subunit (homologue of NR2A) was decreased in the CA2 of hippocampus by citalopram and the epsilon 2 subunit (homologue of NR2B) decreased in CA1-4 of the hippocampus. These changes are in the opposite direction to those caused by ECS treatment in the rat dentate gyrus.…”

Section: Molecular Mechanisms Underlying the Antidepressant Drug Effectmentioning

confidence: 98%

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Antidepressant mechanisms: functional and molecular correlates of excitatory amino acid neurotransmission

Stewart

Reid

2002

Mol Psychiatry

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Specific targeting of the serotonergic and noradrenergic systems for the development of antidepressant compounds has resulted in drugs with more favourable side-effect profiles but essentially no greater efficacy than those compounds discovered more than 40 years ago. Alternative targets are now being considered in the hope that they will have a faster onset of action and be useful for those patients currently unresponsive to conventional treatments. Excitatory amino acid neurotransmission has been attributed various roles in both normal and abnormal brain function. The N-methyl-D-aspartate receptor in particular has long been postulated to play a role in the formation of memories. Major depressive disorder is characterised by alterations in cognitive function, as well as affect. Although there is evidence that early adverse events and stress can have a causal influence on depression, the underlying neurobiology of the disorder is poorly understood. This review will document current evidence for the involvement of excitatory amino acid neurotransmission in the pathophysiology of the affective disorders. The preclinical literature suggests that both electroconvulsive stimulation and antidepressant drugs can affect hippocampal long-term potentiation and the expression of excitatory amino acid receptor subtypes. Exposing animals to stress, including the kind that produces learned helplessness, can also affect synaptic plasticity in the hippocampus. There is clinical evidence that patients with chronic depression have structural brain abnormalities, including hippocampal atrophy, and a preliminary study has shown that an N-methyl-D-aspartate receptor antagonist may have antidepressant efficacy. Molecular Psychiatry (2002) 7, S15-S22.

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“…Thus, the sustained induction of Narp could mediate the alterations in synaptic responsiveness of dentate granule cells to the perforant path input induced by repeated ECS (Stewart and Reid 1993). In this context, it is also interesting that repeated ECS leads to a marked increase in the expression of GluR1 mRNA in hippocampal neurons (Naylor et al 1996). Thus, increased Narp expression may be needed to localize newly synthesized AMPA receptors at synaptic sites.…”

Section: Discussionmentioning

confidence: 99%

Sustained Increase in Narp Protein Expression Following Repeated Electroconvulsive Seizure

Reti¹,

Baraban²

2000

Neuropsychopharmacology

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The delayed response to many psychiatric treatment regimens has focused attention on identifying enduring changes in gene expression following repeated stimulation that may contribute to these responses. Recent studies have identified Narp protein as a neuronal immediate early gene product that remains elevated in the hippocampus nearly 24 hours after a single episode of electroconvulsive seizure (ECS). To examine how Narp expression responds to repeated stimulation, we have examined the effect of repeated ECS on Narp expression in the hippocampusA central focus of current research in psychopharmacology is to understand the molecular alterations that underlie the long-term effects of psychiatric treatments. Accordingly, there has been intense interest in identifying slowly developing or prolonged changes in gene expression that are induced by repeated administration of psychotropic drugs or ECT (Hyman and Nestler 1996). Although a single ECS episode triggers a rapid induction of multiple immediate early genes (IEG), in most cases examined to date, the expression of these IEGs follows a rapid and transient time course making it unclear whether they contribute to long-term changes elicited by these treatments. Two notable exceptions to this pattern are ⌬ Fos B (Chen et al. 1997;Hiroi et al. 1998) and BDNF (Duman andNibuya et al. 1995;Zetterstrom et al. 1998), which display enduring changes in expression following chronic treatment regimens.In recent studies, Narp has been identified as an IEG product that also displays an atypical, sluggish time course of expression, as it takes 4-8 hours to reach peak levels and remains elevated for nearly 24 hours after a single ECS (O'Brien et al. 1999;Tsui et al. 1996). Functional analysis of Narp has provided compelling evidence that it regulates clustering of AMPA receptors at synaptic sites and may therefore contribute to alterations in excitatory synaptic transmission induced by neuronal stimulation. Both the distinctive time course displayed by Narp and its link to synaptic plasticity make it an attractive candidate gene that might mediate long-term effects of psychiatric treatments. Accordingly, as an initial step in examining how its expression is affected by repeated stimulation, we have monitored the expression of Narp protein following repeated ECS. MATERIALS AND METHODSMaximal ECS was administered to male Sprague-Dawley rats (175-200 g) (Harlan, Indianapolis, IN) as described in Cole et al. (1990). Sham treated rats were handled identically to those receiving ECS except for administration of the electrical current. For repeated ECS, stimulation was administered at 48 hour intervals.To monitor Narp protein levels at various times after single or repeated ECS, animals were killed by decapitation with a small animal guillotine. Hippocampal tissues were dissected and then placed in Laemmli sample buffer (BioRad, Hercules, CA) with additional SDS (3% final concentration). Samples were homogenized, then heated for 1 minute at 65 Њ C. Except where explicitly stated, highe...

show abstract

Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus

Cited by 45 publications

References 26 publications

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

Antidepressant mechanisms: functional and molecular correlates of excitatory amino acid neurotransmission

Sustained Increase in Narp Protein Expression Following Repeated Electroconvulsive Seizure

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