Effect of modafinil on learning performance and neocortical long-term potentiation in rats

Burgos, Héctor; Castillo, Amparo; Flores, Osvaldo; Puentes, Gustavo Cortés; Morgan, Carlos; Gatica, Arnaldo; Cofré, Cristian; Hernández, Alejandro; Laurido, Claudio; Constandil, Luís

doi:10.1016/j.brainresbull.2010.08.010

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…These findings suggest that the pre-training acute administration of MOD promoted emotional memory deficits in an inverted-U shape fashion. Notwithstanding our findings are not in agreement with previous studies in rodents (Béracochéa et al, 2001(Béracochéa et al, , 2002(Béracochéa et al, , 2003(Béracochéa et al, , 2008Morgan et al, 2007;Piérard et al, 2006Piérard et al, , 2007Piérard et al, , 2011Tsanov et al, 2010;Ward et al, 2004), but they seem to be in line with other studies describing no effects (Waters et al, 2005) or even MOD-induced deleterious effects (Burgos et al, 2010;Shuman et al, 2009) on memory. In this way, Shuman et al (2009) have verified that pre-training 75 mg/kg MOD disrupted contextual-fear whereas it did not impair cued-fear conditioning or benefitted performance of mice in the Morris water maze.…”

Section: Discussioncontrasting

confidence: 52%

Inhibitory effects of modafinil on emotional memory in mice

et al. 2013

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Section: Discussioncontrasting

confidence: 52%

Inhibitory effects of modafinil on emotional memory in mice

et al. 2013

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“…Chronic MO treatment impairs PFC dependent learning tasks and PFC-LTP, whereas it decreases reference memory errors in a Olton 4x4 maze, representing the long-term memory and hippocampus dependent component of the task [40]. …”

Section: Discussionmentioning

confidence: 99%

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

et al. 2017

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Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

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“…Furthermore, the drug was able to augment both, postsynaptic responsiveness and theta rhythm in dentate gyrus after a single application (Tsanov et al, 2010 ). Another study revealed that MO decreased long term memory errors in the Olton 4 × 4 maze, which infers that the drug exerts a positive effect on the visuo-spatial task that is hippocampus dependent (Burgos et al, 2010 ).…”

Section: Discussionmentioning

confidence: 95%

Differential effects of wake promoting drug modafinil in aversive learning paradigms

Shanmugasundaram

Korz

Fendt

et al. 2015

Front. Behav. Neurosci.

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Modafinil (MO) an inhibitor of the dopamine transporter was initially approved to treat narcolepsy, a sleep related disorder in humans. One interesting “side-effect” of this drug, which emerged from preclinical and clinical studies, is the facilitation of cognitive performance. So far, this was primarily shown in appetitive learning paradigms, but it is yet unclear whether MO exerts a more general cognitive enhancement effect. Thus, the aim of the present study in rats was to extend these findings by testing the effects of MO in two aversive paradigms, Pavlovian fear conditioning (FC) and the operant two-way active avoidance (TWA) learning paradigms. We discovered a differential, task-dependent effect of MO. In the FC paradigm MO treated rats showed a dose-dependent enhancement of fear memory compared to vehicle treated rats, indicated by increased context-related freezing. Cue related fear memory remained unaffected. In the TWA paradigm MO induced a significant decrease of avoidance responses compared to vehicle treated animals, while the number of escape reactions during the acquisition of the TWA task remained unaffected. These findings expand the knowledge in the regulation of cognitive abilities and may contribute to the understanding of the contraindicative effects of MO in anxiety related mental disorders.

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Effect of modafinil on learning performance and neocortical long-term potentiation in rats

Cited by 19 publications

References 42 publications

Inhibitory effects of modafinil on emotional memory in mice

Inhibitory effects of modafinil on emotional memory in mice

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

Differential effects of wake promoting drug modafinil in aversive learning paradigms

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