Excitatory amino acids and modafinil-induced motor hyperactivity in mice

Modafinil is a synthetic psychostimulant used in the treatment of narcoleps y and idiopathic hypersomnia, without interfering with nocturnal sleep and without amphetamine-like side-effects. In mice, modafinil induces hyperacti vity. We have previously demonstrated that the mechanism of action of modaf inil may involve excitatory amino acids (EAA) and their receptors, particul arly N-methyl-D-aspartic acid (NMDA) subtypes, thus conferring on modafinil neuroprotective properties. However, the precise mechanisms of action of m odafinil remain to be elucidated. Accordingly, since EAA are involved in mo tor integration processes, we have investigated the question of whether mod afinil-induced hyperactivity in mice can be counteracted by propentofylline , an indirect inhibitor of EAA release. We used a behavioural approach base d on actimetry, consisting of image analyses after video recording of the a nimals' movements in their cages in order to quantify their level of activi ty. There were, apparently, no significant differences between the modafini l control group (30 mg/kg, i.p.) and the group treated with propentofylline (2 X 20 mg/kg, i.p.) 30 min and immediately before modafinil administratio n. Excitatory amino acids thus do not seem to be involved in modafinil-indu ced hyperactivity. Med Sci Res 27:153-155 (C) 1999 Lippincott Williams & Wi lkins.