Behavioural and transcriptional effects of escitalopram in the chronic escape deficit model of depression

Benatti, Cristina; Alboni, Silvia; Blom, Johanna Maria Catharina; Gandolfi, Francesco; Mendlewicz, Julien; Brunello, Nicoletta; Tascedda, Fabio

doi:10.1016/j.bbr.2014.06.040

Cited by 11 publications

(14 citation statements)

References 60 publications

(87 reference statements)

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“…Over time the control animals revealed a similar resistance to extinction of burying despite becoming familiar with the marbles. Finally, there was no obvious relation in our study between MB and time in the center arena of our open field, a measure of anxiety (Benatti et al 2014). That measure indicated females administered diazepam were least anxious, but escitalopram females were the most anxious.…”

Section: Discussionmentioning

confidence: 64%

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Marble burying as compulsive behaviors in male and female mice

Taylor¹,

Lerch²,

Chourbaji³

2017

Acta Neurobiologiae Experimentalis

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Marble burying is considered an, albeit controversial, animal model of the compulsive like behaviors of obsessive-compulsive disorder (OCD). Hallmark features of OCD patients are similarities and, more prominent, differences from anxiety disorders, e.g., the absence of sex differences and resistance to spontaneous remission. We report an experiment on marble burying by male and female C57/BL6/N mice. Animals were administered either the classic anxiolytic drug, diazepam, that targets the GABA receptor or a "pure" inhibitor of the serotonin transporter, escitalopram, that has been reported to be particularly effective in OCD. A burying paradigm that more precisely mimics the human condition was used, e.g., testing in the home environment, chronic drug exposure and acknowledging individual differences by pre-selecting for high marble burying. Results were that there were no sex differences in groups treated with drugs or in control mice. Both diazepam and escitalopram decreased numbers of marbles buried compared to vehicle-only controls in the absence of correlated changes in anxiety. Diazepam, however, was more effective than escitalopram in suppressing MB. The conclusion is that along with serotonin, GABA is involved in regulating compulsive behaviors. The marble burying paradigm may prove more useful for pharmacological drugs tests of impulsivity or attention deficit because of the involvement of serotonin and GABA in both disorders.

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Section: Discussionmentioning

confidence: 64%

“…Also recorded was time spent in the center quadrant of the apparatus. The open field is a marker of activity changes under drug influences and time in the central area relative to the other areas adjacent to the walls serves as a measure of anxiety (Archer et al 1987, Benatti et al 2014, Ene et al 2016.…”

Section: Methodsmentioning

confidence: 99%

Marble burying as compulsive behaviors in male and female mice

Taylor¹,

Lerch²,

Chourbaji³

2017

Acta Neurobiologiae Experimentalis

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“…It is predicted that by 2030 depression will become the foremost contributor to the worldwide burden of disease (2). At present, oral administration is the main route to treat depression and patients are required to keep taking medicine everyday for a very long time, which greatly increases the mental burden of patients.…”

Section: Introductionmentioning

confidence: 99%

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

et al. 2016

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Abstract. In order to regulate the skin permeation rate (flux) of escitalopram (ESP), ion-pair strategy was used in our work. Five organic acids with different physicochemical properties, benzoic acid (BA), ibuprofen (IB), salicylic acid (SA), benzenesulfonic acid (BSA), and p-aminobenzoic acid (PABA), were employed as counter-ions to regulate the permeation rate of ESP across the rabbit abdominal skin in vitro. The interaction between ESP and organic acids was characterized by FTIR and 13 C NMR spectroscopy. Results showed that all organic acids investigated in this study performed a controlling effect on ESP flux. To further analyze the factors concerned with the permeation capability of ESP-acid complex, a multiple linear regression model was used. It is concluded that the steady-state flux (J) of ESP-acid complexes had a positive correlation with log K o/w (the n-octanol/water partition coefficient of ion-pair complex) and pK a (the acidity of organic acid counter-ion), but a negative correlation with MW (the molecular weight of ionpair complex). The logK o/w of ion-pair complex is the primary one in all the factors that influence the skin permeation rate of ESP. The results demonstrated that organic acid with appropriate physicochemical properties can be considered as suitable candidate for the transdermal drug delivery of escitalopram.

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“…Combination of acetylsalicylic acid with fluoxetine (FLX) accelerates and potentiates the effect of the antidepressant alone (Brunello et al, 2006); 2. After 7 days of treatment, escitalopram (ESC) (10 mg/kg) is already effective in restoring the natural tendency to avoid a noxious stimulus in about 50% of stressed rats developing an escape deficit (Benatti et al, 2014); 3. Co-administration of aspirin with ESC increases the treatment response rate to escitalopram at about 75% (Brunello et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…For this purpose, animals developing an escape deficit were treated for a week with escitalopram, tested for their ability to avoid a noxious stimulus and divided in responder and non-responder as previously reported (Benatti et al, 2014). Then, we evaluated the effects of escitalopram on expression of CRH, its receptors (CRHR1 and CRHR2), and heat shock protein 70 (HSP70), and also on glucocorticoid receptor (GR) mRNA and protein levels in the hypothalamus and on circulating corticosterone.…”

Section: Introductionmentioning

confidence: 99%

Molecular changes associated with escitalopram response in a stress-based model of depression

Benatti

Alboni

Blom

et al. 2018

Psychoneuroendocrinology

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Converging evidence points at hypothalamus-pituitary-adrenal (HPA) axis hyperactivity and neuroinflammation as important factors involved in the etiopathogenesis of major depressive disorder (MDD) and in therapeutic efficacy of antidepressants. In this study, we examined the molecular effects associated with a response to a week-long treatment with escitalopram in the chronic escape deficit (CED) model, a validated model of depression based on the induction of an escape deficit after exposure of rats to an unavoidable stress. We confirmed our previous result that a treatment with escitalopram (10mg/kg) was effective after 7days in reverting the stress-induced escape deficit in approximately 50% of the animals, separating responders from non-responders. Expression of markers of HPA axis functionality as well as several inflammatory mediators were evaluated in the hypothalamus, a key structure integrating signals from the neuro, immune, endocrine systems. In the hypothalamus of responder animals we observed a decrease in the expression of CRH and its receptors and an increase in GR protein in total and nuclear extracts; this effect was accompanied by a significant decrease in circulating corticosterone in the same cohort. Hypothalamic IL-1β and TNFα expression were increased in stressed animals, while CXCL2, IL-6, and ADAM17 mRNA levels were decreased in escitalopram treated rats regardless of the treatment response. These data suggest that efficacy of a one week treatment with escitalopram may be partially mediated by a decrease HPA axis activity, while in the hypothalamus the drug-induced effects on the expression of immune modulators did not correlate with the behavioural outcome.

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Behavioural and transcriptional effects of escitalopram in the chronic escape deficit model of depression

Cited by 11 publications

References 60 publications

Marble burying as compulsive behaviors in male and female mice

Marble burying as compulsive behaviors in male and female mice

Regulating the Skin Permeation Rate of Escitalopram by Ion-pair Formation with Organic Acids

Molecular changes associated with escitalopram response in a stress-based model of depression

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