Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats

Reed, Abbey L.; Anderson, Jeffrey C.; Bylund, David B.; Petty, Frederick; Refaey, Hesham El; Happe, H. Kevin

doi:10.1007/s00213-009-1535-2

Cited by 19 publications

(15 citation statements)

References 58 publications

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“…Because previous work has shown that the SSRIs citalopram or escitalopram can reverse the behavioral effects of chronic stress ( e.g. Bhagya et al, 2011; Bondi et al, 2008; Jayatissa et al, 2006; Overstreet et al, 2004; Reed et al, 2009), we sought to determine whether escitalopram could reverse the behavioral consequences of CeA CRF-OE. We hypothesized that CeA CRF-OE would directly elevate behavioral measures of anxiety and that, without the ability to decrease CeA CRF expression, escitalopram would have limited efficacy unless escitalopram was able to act downstream of postsynaptic CRF neurons.…”

Section: Discussionmentioning

confidence: 99%

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

Flandreau

Bourke

Ressler

et al. 2013

Psychoneuroendocrinology

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Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral manifestations of CeA CRF-OE. This may be a potential animal model to study treatment-resistant psychopathologies.

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Section: Discussionmentioning

confidence: 99%

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

Flandreau

Bourke

Ressler

et al. 2013

Psychoneuroendocrinology

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“…The injection volume was 1 ml/kg of body weight. The doses for drugs were chosen based on effective doses used in our previous behavioral observations: NAC (100 mg/kg) (Smaga et al 2012) and URB597 (Adamczyk et al 2008) as well as in other literature findings on IMI (15 mg/kg) (Tokita et al 2012), ESC (10 mg/kg) (Reed et al 2009), and TIA (10 mg/kg) (Whitton et al 1991). …”

Section: Methodsmentioning

confidence: 99%

Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures

et al. 2014

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The endocannabinoid (eCB) system has recently been implicated in both the pathogenesis of depression and the action of antidepressants. Here, we investigated the effect of acutely or chronically administering antidepressants [imipramine (IMI) (15 mg/kg), escitalopram (ESC) (10 mg/kg), and tianeptine (10 mg/kg)] on the levels of both eCBs [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] and N-acylethanolamines (NAEs) [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)] in various rat brain regions. We also examined the ability of the acute and chronic administration of N-acetylcysteine (NAC) (a mucolytic drug; 100 mg/kg) or URB597 (a fatty acid amide hydrolase inhibitor; 0.3 mg/kg), which have both elicited antidepressant activity in preclinical studies, to affect eCB and NAE levels. Next, we determined whether the observed effects are stable 10 days after the chronic administration of these drugs was halted. We report that the chronic administration of all investigated drugs increased AEA levels in the hippocampus and also increased both AEA and 2-AG levels in the dorsal striatum. NAE levels in limbic regions also increased after treatment with IMI (PEA/OEA), ESC (PEA), and NAC (PEA/OEA). Removing chronic ESC treatment for 10 days affected eCB and NAE levels in the frontal cortex, hippocampus, dorsal striatum, and cerebellum, while a similar tianeptine-free period enhanced accumbal NAE levels. All other drugs maintained their effects after the 10-day washout period. Therefore, the eCB system appears to play a significant role in the mechanism of action of clinically effective and potential antidepressants and may serve as a target for drug design and discovery.

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“…The rats were initially placed in 2 groups; a tested control (TC) group, which is restrained with electrodes attached to the tail but not shocked, and an inescapably stressed group (TSS). Twenty-four hours after restraint with or without TSS exposure, rats were divided in two sets, one set of rats tested for escape behavior using a shuttle-box test [23, 24], while the other set of rats were sacrificed before being tested for escape behavior.…”

Section: Methodsmentioning

confidence: 99%

Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: A potential link to stress resilience

Taneja¹,

Salim²,

Saha³

et al. 2011

Behavioural Brain Research

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Exposure of rats to unpredictable, inescapable stress results in two distinct behaviors during subsequent escape testing. One behavior, suggestive of lack of stress resilience, is prolonged escape latency compared to non-stressed rats and is labeled learned helplessness (LH). The other behavior suggestive of stress resilience is normal escape latency and is labeled non-helpless (NH). This study examines the effects of unpredictable, inescapable tail-shock stress (TSS) on alpha2-adrenoceptor (α2-AR) and corticotropin-releasing factor 1 receptor (CRF1) regulation as well as protein levels of G protein-coupled receptor kinase 3 (GRK3), GRK2, tyrosine hydroxylase (TH) plus carbonylated protein levels in locus coeruleus (LC), amygdala (AMG), cortex (COR) and striatum (STR). In NH rats, α2-AR and CRF1 receptors were significantly down-regulated in LC after TSS. No changes in these receptor levels were observed in the LC of LH rats. GRK3, which phosphorylates receptors and thereby contributes to α2-AR and CRF1 receptor down-regulation, was reduced in the LC of LH but not NH rats. GRK2 levels were unchanged. In AMG, GRK3 but not GRK2 levels were reduced in LH but not NH rats, and receptor regulation was impaired in LH rats. In STR, no changes in GRK3 or GRK2 levels were observed. Finally, protein carbonylation, an index of oxidative stress, was increased in the LC and AMG of LH but not NH rats. We suggest that reduced stress resilience after TSS may be related to oxidative stress, depletion of GRK3 and impaired regulation of α2-AR and CRF1 receptor in LC.

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Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats

Cited by 19 publications

References 58 publications

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

Antidepressants and Changes in Concentration of Endocannabinoids and N-Acylethanolamines in Rat Brain Structures

Differential effects of inescapable stress on locus coeruleus GRK3, alpha2-adrenoceptor and CRF1 receptor levels in learned helpless and non-helpless rats: A potential link to stress resilience

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