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

• Published in: Neuropharmacology Vol. 59; no. 1; pp. 9 - 19
• Main Authors: Tsanov, Marian, Lyons, Declan G., Barlow, Sally, González Reyes, Rodrigo E., O’Mara, Shane M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2010
• Subjects: Anesthesia; Animals; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - pharmacology; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Dentate gyrus; Dentate Gyrus - drug effects; Dentate Gyrus - physiology; Electric Stimulation; Excitatory Postsynaptic Potentials - drug effects; Long-term potentiation; Male; Maze Learning - drug effects; Maze Learning - physiology; Modafinil; Motor Activity - drug effects; Neuronal Plasticity - drug effects; Neurons - drug effects; Neurons - physiology; Perforant Pathway - drug effects; Perforant Pathway - physiology; Rats; Rats, Wistar; Synapses - drug effects; Synapses - physiology; Theta oscillation; Theta Rhythm - drug effects; Time Factors; Urethane; Water; Water maze; Dentate gyrus; Modafinil; Theta oscillation; Long-term potentiation; Water maze
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2010.03.010

Modafinil 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 behavioural performance and synaptic plasticity in rats. Improved acquisition in the water maze task was observed in animals that underwent chronic treatment with modafinil. We found that the distance traveled and escape latency were reduced after the first day in chronically-treated rats, compared to controls. Importantly, 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 200 Hz high-frequency stimulation. Furthermore, the modafinil-dependent enhancement of postsynaptic potentials correlated selectively with theta rhythm augmentation. We propose that modafinil may facilitate hippocampal-associated spatial representation via increased theta-related hippocampal plasticity.