Ameliorating effects of aripiprazole on cognitive functions and depressive-like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity

Russo, Emilio; Citraro, Rita; Davoli, Alessandro; Gallelli, Luca; Paola, Eugenio Donato Di; Sarro, Giovambattista De

doi:10.1016/j.neuropharm.2012.06.039

Cited by 73 publications

(75 citation statements)

References 63 publications

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“…Dopaminergic neurotransmission/modulation has been shown to participate in the control of absence seizures (Citraro et al, 2015a;de Bruin et al, 2000;Russo et al, 2013a) very likely through its action on the nigrostriatal pathway and control of the activity of GABAergic neurons in the substantia nigra (Deransart et al, 2000;Warter et al, 1988).…”

Section: Dopaminementioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

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128

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Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.09.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial "insult" responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then nongenetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.

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Section: Dopaminementioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

Self Cite

128

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“…Neither clozapine nor olanzapine treatments affected the incidence and the latency of audiogenic seizures in ethanol-dependent rats [21,22]. Recently, we have reported that aripiprazole, a new atypical AP, was able to reduce absence seizures with positive modulatory actions on depression and anxiety in WAG/Rij rats, an animal model of epilepsy and depression comorbidity [23].…”

Section: Introductionmentioning

confidence: 95%

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

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Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

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“…Aripiprazole has the profile of an atypical agent, with efficacy in the treatment of positive and negative symptoms of psychosis as well as mood symptoms [25]. In a genetic study on rats, the anti-seizure effect of aripiprazole has been demonstrated by positive modulatory actions on depression, anxiety and memory [11]. On the other hand, in the case reports it has been reported that aripiprazole induced seizure twice in adult and once in pediatric patients [12].…”

Section: Discussionmentioning

confidence: 99%

“…The risk of seizures with aripiprazole is reported to be 0.1%, the lowest among atypical agents [10]. A study demonstrated that aripiprazole might have a potential in treating absence seizures but more interestingly, this effect might be accompanied by positive modulatory actions on depression, anxiety and memory, which might be also beneficial in other epileptic syndromes [11]. On the other hand, aripiprazole-induced seizures have been reported twice in adult patients and once in pediatric populations [12].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

et al. 2015

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Almost all antipsychotics have been associated with a risk of epileptic seizure provocation. Aripiprazole is a novel atypical antipsychotic. The risk of seizures with aripiprazole is reported to be the lowest among atypical agents. In this study, we investigated the effect of aripiprazole on seizure of mice in sub-chronic treatments. We also examined the interaction of nitric oxide (NO) with aripiprazole in seizure experiments. Mice received aripiprazole for 6 days and then on the 7th day aripiprazole was injected 60 min before intraperitoneal pentylenetetrazole or electroshock. L-NAME (non-selective NO synthase (NOS) inhibitor), 7-nitroindazole (neuronal NOS selective inhibitor), aminoguanidine (inducible NOS selective inhibitors) or L-arginine (NO donor), all were injected 5 min before aripiprazole in separate groups. The results of both seizure models demonstrated anti-epileptic properties of aripiprazole in sub-chronic administrations. Co-administration of aripiprazole and selective and non-selective NOS inhibitors prevented the anticonvulsant effect of aripiprazole. While L-arginine and aripiprazole co-administration increased the clonic seizure threshold and protection against tonic seizure and death, these effects were not significant. The current results indicated that aripiprazole has anticonvulsant effects probably through the release of NO.

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Ameliorating effects of aripiprazole on cognitive functions and depressive-like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity

Cited by 73 publications

References 63 publications

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

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