MODULATION OF THE STIMULATING EFFECT OF MODAFINIL BY GLUTAMATE AGONISTS AND ANTAGONISTS

Modafinil is a synthetic psychostimulant whose mechanism of action is not completely understood but could imply EAA (excitatory amino acids) receptors. In the present study, we assessed the influence of glutama te agonists and antagonists on modafinil effect using a behavioural ap proach based on actimetry. Adult male mice were given both modafinil ( 100 mg kg(-1)) and one of the following excitatory amino acids structu ral analogues (intraperitoneal route): N-methyl-D-aspartate (NMDA) (5 mg kg(-1)), non-NMDA agonist pha-amino-3-hydroxy-5-methyl-4-isoxazolep ropionate (AMPA) (5 mg kg(-1)), metabotropic agonist trans-1-amino-cyc lopeniane-1,3-dicarboxylate (ACPD) (5 mg kg(-1)), NMDA antagonist MK-8 01 (0.3 mg kg(-1)), non-NMDA antagonist 6,7-dinitroquinoxaline-2,3 dio ne (DNQX) (10 mg kg(-1)) and metabotropic antagonists L-AP4 and L-AP3 (10 mg kg(-1)), as well as glutamate (5 mg kg(-1)). Results were compa red to those obtained with modafinil alone. AMPA, ACPD, MK-801 and L-A P3 enhanced the stimulating effect of modafinil while L-AP4 antagonise d it. NMDA and DNQX did not have a significant effect, neither did glu tamate, probably because its poor penetration of the blood-brain barri er. Our findings suggest a possible role of EAA in modafinil action wh ich requires further evaluation.