Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models

Pereira, Patrı́cia; Gianesini, Janaína; Barbosa, Cibele da Silva; Cassol, Graziela Freitas; Borowski, Rafael Gomes Von; Kahl, Vivian Francília Silva; Cappelari, Shandale Emanuele; Picada, Jaqueline Nascimento

doi:10.1016/j.phrs.2008.09.014

Cited by 26 publications

(15 citation statements)

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“…The cells were also visually scored according to tail 1227 www.chinaphar.com Picada JN et al Acta Pharmacologica Sinica npg size into five classes, ranging from undamaged (0) to maximally damaged (4), resulting in a single DNA damage score for each animal and consequently for each studied group. Therefore, the damage index (DI) can range from 0 (completely undamaged, 100 cells×0) to 400 (with maximum damage, 100 cells×4) [14] . …”

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confidence: 99%

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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Aim: Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D 2 partial agonism, serotonin 5-HT 1A partial agonism and 5-HT 2A antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation. Methods: Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS). Results: Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short-and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected. Conclusion: Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.Keywords: antipsychotic agent; aripiprazole; locomotion; memory; genotoxic/mutagenic activities; DNA damage; lipoperoxidation Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1225Sinica ( -1232 doi: 10.1038/aps.2011 published online 15 Aug 2011 Original Article * To whom correspondence should be addressed. [8] .In the experimental context, Nagai et al [9] showed that aripiprazole that was administered as either a single dose or as consecutive doses (for 7 d) ameliorated phencyclidine-induced impairment of recognition memory in mice. However, another study showed that aripiprazole impaired the passiveavoidance response at doses near its anti-dopamine ED 50 (7.7 mg/kg, as defined by apomorphine stereotypy). At doses lower than those that affected the passive-avoidance response, aripiprazole was unable to reverse the MK-801-induced impairment in the same task [4] . Therefore, further investigations are necessary to elucidate the effect of aripiprazole on memory.The aim of the present study was to investigate the effects of aripiprazole on memory and on locomotor and exploratory activities with the inhibitory avoidance and open field tasks as behavioral models. Some drugs that affect memory can induce damage in biomolecules, such as lipids and DNA. Therefore, possible cytotoxic and genotoxic effects were evaluated by measuring lipid peroxidation in the liver and DNA strand breaks in both the peripheral blood and brain tissues after behavioral tasks. Mutagenic e...

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confidence: 99%

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

et al. 2011

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“…These results suggest that impairment of memory depends on the anticholinergic effect of amitriptyline. Additionally, no impairing effect on memory of the serotonin and noradrenaline re-uptake inhibitors venlafaxine and duloxetine has been reported 55,56 . These drugs are known to have no or minimal anticholinergic effect, and this may contribute to their effect on memory 57,58 .…”

Section: Discussionmentioning

confidence: 99%

Improving Effect of Atomoxetine and Reboxetine on Memory in Passive Avoidance Task

Yüce

İlkaya

Karabekiroğlu

et al. 2014

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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ÖZET:Atomoksetin ve reboksetinin pasif sakınma testinde bellek üzerindeki iyileştirici etkisi Amaç: Serotonin ve/veya noradrenalin geri alım inhibitörlerinin bellek üzerine etkileri çeşitli klinik ve preklinik çalışmalarda araştırılmıştır. Ancak, çelişkili sonuçlar bildirilmiştir. Bu çalışmada selektif noradrenalin geri alım inhibitörü olan atomoksetin ve reboksetinin; serotonin geri alım inhibitörü olan paroksetinin ve trisiklik antidepresan amitriptilinin farelerde bellek üzerindeki etkileri pasif sakınma testi ile karşılaştırılmalı olarak değerlendirilmiştir. Yöntem: Çalışmada 25-30 gr ağırlığında erkek Balb-C fareler kullanıldı. Reboksetin (10 mg/kg), atomoksetin (5 mg/kg), paroksetin (10 mg/kg) ve amitriptilin (10 mg/kg) tek başlarına ve skopolamin (1 mg/kg) ile kombinasyon şeklinde uygulandı. Belleği değerlendirmek için pasif sakınma testi kullanıldı. İlk gün farelerin kazanım süresi (acquisition time) ikinci gün (24 saat sonra) ise retansiyon süresi (retention time) kaydedildi. Tüm ilaçlar ve salin, retansiyon süresinin değerlendirilmesinden 30 dakika önce intraperitoneal olarak uygulandı. Bulgular: Tüm ilaçlar ve salin, tek başlarına uygulandıklarında retansiyon süresini bozmadılar. Ancak, skopolamin retansiyon süresini anlamlı ölçüde bozdu (p=0.003). Skopolamin ile kombine edildiğinde reboksetin, atomoksetin ve paroksetin retansiyon süresinde belirgin bir iyileştirici etki gösterdi. Amitriptilin, skopolamin ile kombine edildiğinde retansiyon süresi anlamlı ölçüde azaldı (p=0.013). Sonuç: Atomoksetin ve reboksetinin bellek bozukluğu üzerindeki iyileştirici etkisi noradrenalin gerialım inhibisyonuna bağlı olabileceği ileri sürülebilir. Bellek bozukluğu üzerinde paroksetinin iyileştirici etkisi artmış serotonerjik aktivite ile ilişkili olabilir. Amitriptilinin bellek bozukluğu üzerinde iyileştirici etkisinin olmaması antikolinerjik yan etkisi nedeniyle olabilir. Bu ilaçların iyileştirici etkilerinin mekanizmalarını açıklamak için aynı model ve hayvan türlerini kullanarak yapılacak daha ileri çalışmalara ihtiyaç vardır. Improving effect of atomoxetine and reboxetine on memory in passive avoidance task Objective: The effects of serotonin and/or noradrenaline re-uptake inhibitors on memory have been investigated in various clinical and pre-clinical studies. However, contradictory results have been reported. In this study, the effect of the selective noradrenaline re-uptake inhibitors atomoxetine and reboxetine, a tricyclic antidepressant, amitriptyline, and a selective serotonin re-uptake inhibitor, paroxetine, on learning and memory were examined alone or in combination with scopolamine in mice using a passive avoidance task. Methods: Male Balb-C mice (25-30 g) were used. Reboxetine (10 mg/kg), atomoxetine (5 mg/kg), paroxetine (10 mg/kg) and amitriptyline (10 mg/ kg) were investigated alone or in combination with scopolamine (1 mg/kg). A passive avoidance task was used to evaluate memory function. Acquisition time was recorded on the first day and retention time on the second (after 24 h). All drugs and sal...

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“…Moreover, memory impairment induced by MK-801, an NMDA antagonist, is unaltered by duloxetine, that is, it is unable to recover the impairment on memory produced by this glutamatergic antagonist [67]. In summary, the effects of duloxetine most closely linked with depression are a reduction in body weight, food intake and, at higher doses, locomotor activity.…”

Section: Antidepressant Activitymentioning

confidence: 98%

“…No effects of duloxetine on short-or long-term memory have been reported in the rat inhibitory avoidance task [67]. Moreover, memory impairment induced by MK-801, an NMDA antagonist, is unaltered by duloxetine, that is, it is unable to recover the impairment on memory produced by this glutamatergic antagonist [67].…”

Section: Antidepressant Activitymentioning

confidence: 99%

Preclinical discovery of duloxetine for the treatment of depression

Torres-Sánchez

Pérez-Caballero

Micó

et al. 2012

Expert Opinion on Drug Discovery

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Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models

Cited by 26 publications

References 32 publications

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

Improving Effect of Atomoxetine and Reboxetine on Memory in Passive Avoidance Task

Preclinical discovery of duloxetine for the treatment of depression

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