Differential effects of modafinil, methamphetamine, and MDMA on agonistic behavior in male mice.
The aim of the present study was to compare the behavioral effects of modafinil, an atypical psychostimulatory acting and cognitive-function improving drug, with the effects of the psychostimulants methamphetamine (MET) and MDMA (3,4-methylenedioxymethamphetamine, or ecstasy) in a model of mouse agonistic behavior. This model enables the observation of ethologically well-defined sociable, timid, aggressive, and locomotor behavioral acts and postures. Singly-housed male mice (isolates) were separated into 4 groups. The observations were performed in 4 sessions, 1 week apart. In each interaction, singly-housed mice were paired with non-aggressive group-housed partners for 4 min in a neutral environment. The isolates received, in a Latin square design, either a) a vehicle or modafinil at doses 2.0, 10.0, or 50.0 mgkg or b) a vehicle or MET at doses 1.0, 5.0, or 10.0 mgkg or c) a vehicle or MDMA at doses 2.5, 10.0, or 30.0 mgkg. The isolates were categorized as timid or aggressive according to their behavior in the control interaction (vehicle pre-treatment). Elements of locomotor, sociable, aggressive, and timid behavior were evaluated (one-way ANOVA). In the aggressive mice, no change in the sum of aggressive behavior was measured following modafinil administration, while both methamphetamine and MDMA produced dose-dependent inhibition of aggression (p<0.01). The substantial difference in the tested drug effects on agonistic behavior was an increased occurrence of sociable acts (p<0.01) accompanied by a simultaneous increase of timid acts (p<0.01) recorded after MDMA, but not after modafinil or methamphetamine administration. In the timid mice, at least some doses of modafinil decreased timidity (p<0.01) and increased aggression (p<0.01) with no effect on sociability. Administration of MDMA increased timid activities (p<0.01). Both MDMA and MET decreased sociability (p<0.01).