Strain-dependent neurochemical and neuroendocrine effects of desipramine, but not fluoxetine or imipramine, in Spontaneously Hypertensive and Wistar–Kyoto rats

Durand, M.; Aguerre, Sylvie; Fernandez, Francesca; Edno, L.; Combourieu, I.; Mormède, Pierre; Chaouloff, Francis

doi:10.1016/s0028-3908(00)00088-5

Cited by 25 publications

(11 citation statements)

References 63 publications

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“…The p K i ratios 5HT 2A /D 2 of 8c and 8b were similar to the value of olanzapine ( P = 0.137 and P = 0.457, respectively). This value ratio is consistent with the previously reported one for olanzapine in the literature [47,49]. Compounds 8a displayed a significant reduction in binding to the D 2 and 5HT 2A receptors ( P = 0.001 and P = 0.001, respectively) receptors.…”

Section: Resultssupporting

confidence: 92%

“…The assays used were standard in vitro radioligand binding assays. Radioligand binding assays were run under the conditions described previously with some modifications [47,48]. The affinities of compound 8c for the D 2 and 5HT 2A receptors were similar to the values found for olanzapine ( P = 0.561 and P = 0.959, respectively) (Table 1).…”

Section: Resultsmentioning

confidence: 66%

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Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

et al. 2012

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BackgroundOlanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios.ResultsWe have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors.ConclusionsWe suggest that thienobenzodiazepines 8b and 8c with lower binding affinity for the H1 receptors, but similar 5HT2A/D2 receptor binding affinity ratios to those of olanzapine. These compounds may offer a better pharmacological profile than olanzapine for treating patients with schizophrenia.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 66%

Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

et al. 2012

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“…Chronic DES treatment (i.e., more than 10 days) not only reduces NET binding, but also alters β- and α-adrenergic receptor binding in a region-specific manner in rats (Hancock and Marsh, 1985; Zhao et al, 2008; Zhang et al, 2009). Treatment with DES at the same dose that altered NE receptor and NET (i.e., 10 mg/kg/day) blocked stress – and alcohol-induced anxiety-like behavior in WKY rats (Durand et al, 2000; Getachew et al, 2008). Thus, DES administration was expected to improve extinction in WKY rats, possibly through pharmacological changes in the NE system.…”

Section: Discussionmentioning

confidence: 99%

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Jiao

Beck

Stewart

et al. 2014

Front. Behav. Neurosci.

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Avoidance and its perseveration represent key features of anxiety disorders. Both pharmacological and behavioral approaches (i.e., anxiolytics and extinction therapy) have been utilized to modulate avoidance behavior in patients. However, the outcome has not always been desirable. Part of the reason is attributed to the diverse neuropathology of anxiety disorders. Here, we investigated the effect of psychotropic drugs that target various monoamine systems on extinction of avoidance behavior using lever-press avoidance task. Here, we used the Wistar-Kyoto (WKY) rat, a unique rat model that exhibits facilitated avoidance and extinction resistance along with malfunction of the dopamine (DA) system. Sprague Dawley (SD) and WKY rats were trained to acquire lever-press avoidance. WKY rats acquired avoidance faster and to a higher level compared to SD rats. During pharmacological treatment, bupropion and desipramine (DES) significantly reduced avoidance response selectively in WKY rats. However, after the discontinuation of drug treatment, only those WKY rats that were previously treated with DES exhibited lower avoidance response compared to the control group. In contrast, none of the psychotropic drugs facilitated avoidance extinction in SD rats. Instead, DES impaired avoidance extinction and increased non-reinforced response in SD rats. Interestingly, paroxetine, a widely used antidepressant and anxiolytic, exhibited the weakest effect in WKY rats and no effects at all in SD rats. Thus, our data suggest that malfunctions in brain catecholamine system could be one of the underlying etiologies of anxiety-like behavior, particularly avoidance perseveration. Furthermore, pharmacological manipulation targeting DA and norepinephrine may be more effective to facilitate extinction learning in this strain. The data from the present study may shed light on new pharmacological approaches to treat patients with anxiety disorders who are not responding to serotonin re-uptake inhibitors.

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“…Chronic administration of tricyclics, such as desipramine, improves most of the “depressive-like” symptoms exhibited by WKY adult rats [55, 75]. Other studies showed that selective 5HT reuptake inhibitors such as fluoxetine, only affect a portion of the serotonin-receptor binding capacity in the brain [56, 57].…”

Section: Discussionmentioning

confidence: 99%

“…The dose of the antidepressant treatments was chosen according to several studies conducted on adult rats from this strain [55–57]. Different doses were used in these studies ranging from 5–10 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression—An Animal Model Study

Malkesman

Asaf

Shbiro

et al. 2009

Advances in Pharmacological Sciences

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Basal levels of monoamines and DHEA in four main limbic brain regions were measured in prepubertal Wistar Kyoto (WKY) rats (a putative animal model of childhood depression). Basal levels of “Brain-Derived Neurotrophic Factor (BDNF)” were also determined in two regions in the hippocampus, compared with Wistar strain controls. In the second phase, we examined the responsiveness of prepubertal WKY rats to different types of chronic antidepressant treatments: Fluoxetine, Desipramine, and dehydroepiandrosterone sulfate (DHEAS). WKY prepubertal rats exhibited different monoamine levels in the limbic system, reduced DHEA levels in the VTA and lower levels of BDNF in the hippocampus CA3 region compared to controls. In prepubertal WKY rats, only treatment with DHEAS produced a statistically significant decrease in immobility, compared to saline-administered controls in the forced swim test. Wistar controls were not affected by any antidepressant. The results imply that DHEA(S) and BDNF may be involved in the pathophysiology and pharmacotherapy of childhood depression.

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Strain-dependent neurochemical and neuroendocrine effects of desipramine, but not fluoxetine or imipramine, in Spontaneously Hypertensive and Wistar–Kyoto rats

Cited by 25 publications

References 63 publications

Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio

Effects of Psychotropic Agents on Extinction of Lever-Press Avoidance in a Rat Model of Anxiety Vulnerability

Monoamines, BDNF, Dehydroepiandrosterone, DHEA-Sulfate, and Childhood Depression—An Animal Model Study

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