The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus

Abstract

, S.M. The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus, Neuropharmacology (2010Neuropharmacology ( ), doi: 10.1016Neuropharmacology ( /j.neuropharm.2010 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. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTThe psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT AbstractModafinil is a psychostimulant drug used widely for the treatment of narcolepsy, which also has additional positive effects on cognition. Here, we investigate the effects of modafinil on behavioral performance and synaptic plasticity in rats.Improved acquisition of water maze task was observed for animals that underwent chronic treatment with modafinil. We found that the distance travelled and escape latency were reduced after the first day in chronically-treated rats, compared to controls. Importantly, the swim velocity was similar for both groups, excluding pharmacological effects on motor skills. We also found that modafinil increases synaptic plasticity in the dentate gyrus of urethane-anaesthetized rats; modafinil induced a robust augmentation of the population spike, evident after application of 2 bursts of 200Hz, high-frequency stimulation. Furthermore, the modafinil-dependent enhancement of postsynaptic potentials correlated selectively with theta rhythm augmentation. We propose that modafinil may facilitate spatial orientation via increased theta-related hippocampal plasticity.

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

“…The fronto-cortical activation is also consistent with the improved cognitive performance observed in rodent behavioral tasks upon MOD administration at doses similar to those employed in the present study (Tsanov et al, 2007;Beracochea et al, 2001Beracochea et al, , 2003Dawson et al, 2010). Consistent with the notion that fronto-cortical cognitive tasks are subserved by an extensively interconnected network of regions (reviewed by Mesulam, 1990), additional brain substrates activated by MOD may have a role in the pro-cognitive action of the drug.…”

Inhibitory effects of modafinil on emotional memory in mice

“…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.…”

Modafinil-Induced Changes in Functional Connectivity in the Cortex and Cerebellum of Healthy Elderly Subjects

“…The notion is supported by preclinical evidence showing that modafinil, through increased dopaminergic and noradrenergic transmission, promotes adult neurogenesis, especially within the hippocampus (Brandt et al, 2014). Furthermore, in preclinical models, modafinil has been shown to improve spatial learning and fear conditioning, inhibitory control, WM functioning, and sustained attention (Morgan et al, 2007; Shuman et al, 2009; Tsanov et al, 2010). Our studies provide some FC evidence that corroborates the hypothesis that modafinil may interfere with some of these cognitive domains.…”

“…Furthermore, in preclinical settings, the drug has been shown to promote hippocampal neurogenesis (Brandt et al, 2014) and synaptic plasticity (Rao et al, 2007; Tsanov et al, 2010). Overall, this psychostimulant has been viewed as a CED with lower risks of inducing addiction and a favorable side effect profile (Malcolm et al, 2002).…”