Inhibitory effects of modafinil on emotional memory in mice

Fernandes, H.A.; Zanin, Karina A.; Patti, Camilla L.; Wuo-Silva, Raphael; Carvalho, Reinaldo de Amorim; Fernandes-Santos, Luciano; Bittencourt, Lia; Tufik, Sérgio; Frussa‐Filho, Roberto

doi:10.1016/j.neuropharm.2012.06.058

Cited by 7 publications

(8 citation statements)

References 50 publications

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“…As described elsewhere (Fernandes et al, 2013), the apparatus employed in the plus-maze discriminative avoidance task (PM-DAT) is a modified elevated plus-maze made of wood. The apparatus has two enclosed arms with sidewalls and no top (28.5 × 7 × 18.5 cm).…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimerâ€™s disease

Garcia

Ornellas

Martin

et al. 2014

Front. Aging Neurosci.

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145

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Alzheimer’s disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (Aβ) deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and Aβ plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.

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Section: Methodsmentioning

confidence: 99%

Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimerâ€™s disease

Garcia

Ornellas

Martin

et al. 2014

Front. Aging Neurosci.

Self Cite

145

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show abstract

“…Modafinil vehicle was used as the control solution and administered i.p. This dose range was selected based on previous work of our group (11,18).…”

Section: Methodsmentioning

confidence: 99%

“…In this way, a study conducted by Shuman et al (10) reported that the administration of modafinil immediately after training had no effects on either cued or contextual fear paradigms. In contrast, we have recently demonstrated that the post-training acute administration of modafinil impaired memory consolidation in mice subjected to the plus-maze discriminative avoidance task (11).…”

Section: Introductionmentioning

confidence: 95%

Effects of post-training modafinil administration in a discriminative avoidance task in mice

Fernandes

Zanin

Patti

et al. 2015

Acta Neuropsychiatr.

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“…The effects of modafinil (0, 32, 64 mg/kg) were assessed in a separate group of mice (Cohort 2, N = 20) (all Tocris, UK). Doses of SB242084 (s.c., administered immediately prior to test), 8-OH-DPAT (i.p., administered 20 min prior to test) and modafinil (i.p., 30 min before test) were based on previous studies (Humby et al 2013;Fernandes et al 2013;Rogers et al 2013). Drugs were prepared fresh in physiological saline each day.…”

Section: Task Manipulationsmentioning

confidence: 99%

Effects of 5-HT2C, 5-HT1A receptor challenges and modafinil on the initiation and persistence of gambling behaviours

et al. 2020

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Rationale Problematic patterns of gambling are characterised by loss of control and persistent gambling often to recover losses. However, little is known about the mechanisms that mediate initial choices to begin gambling and then continue to gamble in the face of losing outcomes. Objectives These experiments first assessed gambling and loss-chasing performance under different win/lose probabilities in C57Bl/6 mice, and then investigated the effects of antagonism of 5-HT 2C R with SB242084, 5-HT 1A R agonism with 8-OH-DPAT and modafinil, a putative cognitive enhancer. Results As seen in humans and other species, mice demonstrated the expected patterns of behaviour as the odds for winning were altered increasing gambling and loss-chasing when winning was more likely. SB242084 decreased the likelihood to initially gamble, but had no effects on subsequent gambling choices in the face of repeated losses. In contrast, 8-OH-DPAT had no effects on choosing to gamble in the first place, but once started 8-OH-DPAT increased gambling choices in a dose-sensitive manner. Modafinil effects were different to the serotonergic drugs in both decreasing the propensity to initiate gambling and chase losses. Conclusions We present evidence for dissociable effects of systemic drug administration on different aspects of gambling behaviour. These data extend and reinforce the importance of serotonergic mechanisms in mediating discrete components of gambling behaviour. They further demonstrate the ability of modafinil to reduce gambling behaviour. Our work using a novel mouse paradigm may be of utility in modelling the complex psychological and neurobiological underpinnings of gambling problems, including the analysis of genetic and environmental factors.

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Inhibitory effects of modafinil on emotional memory in mice

Cited by 7 publications

References 50 publications

Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimerâ€™s disease

Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimerâ€™s disease

Effects of post-training modafinil administration in a discriminative avoidance task in mice

Effects of 5-HT2C, 5-HT1A receptor challenges and modafinil on the initiation and persistence of gambling behaviours

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