Modafinil-induced modulation of working memory and plasma corticosterone in chronically-stressed mice

Abstract

The original aims of our study were to investigate the dose-effect relationship of modafinil administration on working memory performance, in parallel with the measurement of plasma corticosterone in chronically-stressed mice, as compared to control mice. Memory performance was evaluated by spontaneous alternation in a T-maze. Vehicle or modafinil (8, 16 or 32 mg/kg) were administered after or without chronic stress (immobilization and exposure to light) for 15 min/day over a period of consecutive 14 days. Immediately after behavioral testing, blood was sampled to measure plasma corticosterone levels. Under non-stress conditions, corticosterone significantly increased with 16 and 32 mg/kg modafinil administration. Interestingly, optimal working memory performance was revealed at the 16 mg/kg dose. Moreover, no correlation was evidenced between working memory performance and plasma corticosterone level in modafinil-treated animals. Under stress conditions, corticosterone level was lowered at 8 mg/kg and remained unchanged at 16 and 32 mg/kg modafinil. An optimal working memory performance was evidenced at 8 mg/kg, which indicated a decrease in the efficiency threshold of modafinil under stress. Furthermore, an inverse correlation emerged between working memory performance and corticosterone level. Our study evidenced for the first time the interaction between stress and memory, in the emotional modulation of working memory performance, as a function of the administered dose of modafinil.

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

“…Modafinil treatment enhances working memory performance in mice (Pierard et al, 2006) and rats (Ward et al, 2004). In contrast, modafinil did not alter the performance on five-choice serial reaction time in rats (Waters et al, 2005).…”

How to Keep the Brain Awake? The Complex Molecular Pharmacogenetics of Wake Promotion

“…These high-frequency components have been reported to be associated with the presentation of meaningful stimuli, with attentional processes and voluntary movements, and have been suggested to represent a correlate of cognition and synaptic plasticity (Canolty et al, 2006;Crone et al, 2006;Gray and Singer, 1989;Sanes and Donoghue, 1993;Tiitinen et al, 1993;Traub et al, 2005). The enhanced gamma activity observed during druginduced wakefulness might thus reflect heightened cognitive performance and, at least for modafinil, an increase in working memory has been demonstrated in mice (Beracochea et al, 2001(Beracochea et al, , 2002(Beracochea et al, , 2003Pierard et al, 2006) and rats (Miller et al, 2000;Ward et al, 2004). Other corroborating observations come from the increased c-FOS activity in the hippocampus of B6 mice, which was largest for the drug that also induced the largest increase in gamma activity; that is YKP10A.…”

The Neuronal Expression of MYC Causes a Neurodegenerative Phenotype in a Novel Transgenic Mouse

“…Task achievement time (how long it took the animal to enter a goal arm after the gate opened) was also calculated. 22 Statistical comparisons were performed by parametric analysis using a one-way analysis of variance and/or Student's t-test, as appropriate, to determine significant differences across genotypes. The null hypothesis was rejected at P Ͻ 0.05.…”