Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: Role of serotonin synthesis

Bosker, Fokko J.; Tanke, Marit A.C.; Jongsma, Minke E.; Cremers, Thomas; Jagtman, Evelien; Pietersen, Charmaine Y.; Hart, Marieke G. C. van der; Gladkevich, Anatoliy V.; Kema, Ido P.; Westerink, Ben H.C.; Korf, Jakob; Boer, Johan A. den

doi:10.1016/j.neuint.2010.10.001

Cited by 30 publications

(34 citation statements)

References 79 publications

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“…Exaggerated acoustic startle response has been previously linked to anxiety-like behaviors in rodents (Plappert and Pilz, 2002). Therefore, the findings of Bosker et al (2010) suggest a higher level of anxiety in the citalopram discontinuation group, which is similar to the increased incidence of anxiety in patients with the SSRI discontinuation syndrome. An increased reactivity to acoustic stimuli in rats has been linked to long-term depletion of serotonin in the brain (Tanke et al, 2008).…”

Section: Animal Studiesmentioning

confidence: 74%

“…An increased reactivity to acoustic stimuli in rats has been linked to long-term depletion of serotonin in the brain (Tanke et al, 2008). Consistent with that notion, Bosker et al (2010) found that an index of serotonin turnover [the ratio of 5-hydroxyindoleacetic acid to serotonin (5-HIAA/5-HT)] was increased after the 48-h washout period following chronic citalopram treatment, while chronic treatment exerted no significant effect on serotonin turnover. This finding is in agreement with an earlier study reporting that levels of the serotonin metabolite 5-HIAA are increased during withdrawal from chronic fluoxetine (30 mg/kg/days for 21 days), and are sustained at levels exceeding control levels (by 30–50%) for at least 14 days after cessation of chronic fluoxetine treatment (Trouvin et al, 1993).…”

Section: Animal Studiesmentioning

confidence: 81%

“…In an attempt to compare and contrast the mechanisms underlying the effects of continuous SSRI administration against abrupt SSRI discontinuation, Bosker and colleagues measured the acoustic startle response of rats that had either been receiving 2 weeks of citalopram or had undergone 48 h of discontinuation from citalopram treatment (Bosker et al, 2010). Behavioral assessments started 2 days after the removal of osmotic mini pumps filled with either saline or 50 mg/ml citalopram.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Behavioral changes in relation to increased serotonin turnover rates during drug washout were not examined. Similarly, as Bosker et al (2010) assessed the biochemical consequences and behavioral effects of citalopram discontinuation in separate cohorts of animals, no direct comparisons between increased serotonin turnover and increased acoustic startle response could be made. Further behavioral testing is required to validate the finding of a greater acoustic startle response, using additional tests such as the elevated-plus maze, the light-dark box, etc.…”

Section: Animal Studiesmentioning

confidence: 99%

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Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Renoir¹

2013

Front. Pharmacol.

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Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1–7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition.

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Section: Animal Studiesmentioning

confidence: 74%

Section: Animal Studiesmentioning

confidence: 81%

Section: Animal Studiesmentioning

confidence: 99%

Section: Animal Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Renoir¹

2013

Front. Pharmacol.

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“…This result suggests that other pathways might be interacting with 5-HT, as has also been implied by the results of other studies [37,38]. However, care should be taken when considering this possibility because the model cannot consider the effects of 5-HT concentration on its homeostasis.…”

Section: Resultsmentioning

confidence: 68%

Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

Moreno-Ramos

Lattig

Barrios

2013

Theor Biol Med Model

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Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT synthesis.

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Effects of an antidepressant mixture on the brain serotonin and predation behavior of hybrid striped bass

Bisesi

Sweet

Hurk

et al. 2015

Enviro Toxic and Chemistry

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Antidepressants have been found in measurable concentrations in final treated wastewater effluent and receiving waters throughout the world. Studies have shown that these concentrations are typically not overtly toxic, but the psychotropic mode of action of these chemicals warrants examination of their behavioral effects. Exposure of hybrid striped bass to the antidepressants fluoxetine or venlafaxine alone has been shown to cause decreased brain serotonin levels and increased time to capture prey at concentrations typically 1 to 2 orders of magnitude higher than environmentally relevant concentrations. In the present study, equally effective doses of fluoxetine and venlafaxine were used to perform a mixture study, using a toxic unit approach to determine whether these antidepressants may act in an additive manner at lower concentrations. The results indicated that mixtures of these antidepressants caused decreased brain serotonin and increased time to capture prey at concentrations lower than reported in previous studies. Low concentration mixtures caused an additive effect on brain serotonin levels and time to capture prey, whereas higher concentrations were less than additive. The results were consistent with the dose addition concept, with higher concentration mixtures potentially saturating the effects on serotonin in the brain. Results from the present study indicate that antidepressants have the potential to be additive on the biochemical and individual scale, which necessitates more robust analysis of antidepressant mixtures and their potential to act together in low concentration scenarios.

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Biochemical and behavioral effects of long-term citalopram administration and discontinuation in rats: Role of serotonin synthesis

Cited by 30 publications

References 79 publications

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved

Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

Effects of an antidepressant mixture on the brain serotonin and predation behavior of hybrid striped bass

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