LACK OF PRESYNAPTIC DOPAMINERGIC INVOLVEMENT IN MODAFINIL ACTIVITY INANESTHETIZED MICE - IN-VIVO VOLTAMMETRY STUDIES

Modafinil was compared to the indirect dopaminergic drugs, dexamphetam ine and methylphenidate, using in vivo differential normal pulse volta mmetry with carbon fibre electrodes located in the caudate nucleus to study extracellular catechol level in anaesthetized mice. Modafinil (1 6-256 mg kg(-1)) failed to modify the catechol oxidation peak height ( peak 2). Dexamphetamine at low doses (2 and 4 mg kg(-1)) decreased, wh ile at a higher dose (8 mg kg(-1)) did not modify peak 2 height. A low dose of methylphenidate (16 mg kg(-1)) did not display any effect, wh ile higher doses (32 and 64 mg kg(-1)) increased peak 2 height. Pargyl ine-induced monoamine oxidase inhibition elicited a rapid and dramatic decrease in peak 2 height (related to the decrease of catechol levels ). In these conditions modafinil (64 and 256 mg kg(-1)) did not modify , while dexamphetamine (2, 4 and 8 mg kg(-1)) and methylphenidate (16, 32 and 64 mg kg(-1)) increased peak 2 height in relation to synaptic dopamine level increase. This study, in mice, demonstrated the lack of effects of modafinil on nigro-striatal function, at the pre-synaptic level, as opposed to dexamphetamine and methylphenidate.