[A unique psychopharmacologic profile of adrafinil in mice].

Abstract

The following psychopharmacological effects of adrafinil have been observed in mice: increase in locomotor activity (64-256 mg.kg-1), antagonism (16-128 mg.kg-1) of the hypnotic effects of barbitone but not of pentobarbitone, reduction of immobility duration in the forced swimming test (16-256 mg.kg-1); slight antagonism (256 mg.kg-1) of electroshock-induced convulsions; no modification of rectal temperature; no stereotyped or climbing behaviour; no increase in lethality in aggregated mice (LD50 isolated = 1022 mg.kg-1, LD50 aggregated = 859 mg.kg-1); lack of effects on the provisional tests for antidepressants: no interaction with reserpine-, oxotremorine-, or apomorphine-induced hypothermia but potentiation of yohimbine-induced toxicity; lack of peripheral sympathetic effects (no mydriasis, no salivation, no contraction of the pilomotor muscles, no antagonism of reserpine-induced ptosis); lack of peripheral anticholinergic effects (no mydriasis, no antagonism of oxotremorine-induced salivation or lacrimation). As compared to no analeptic, anticholinergic or antidepressant drugs, adrafinil shows a unique behavioural profile in mice defined on the one hand by a specific stimulant activity associated with antidepressant-like effects that do no seem related to a beta-adrenergic mechanism and on the other hand by a lack of dopaminergic effects. Most adrafinil-induced effects (increase in locomotor activity, reduction of immobility duration in the forced swimming test) may correspond to a central alpha 1-adrenergic stimulation, but the unexpected lack of peripheral sympathetic effects remains unexplained.