EXPLORING MODAFINIL NEUROPROTECTIVE EFECTS ON METHAMPHETAMINE ACUTE TOXIC DOSE

BISAGNO V., RAINERI, M., PESKIN V., URBANO, F.J., WIKINSKI S.I

Rosario, Argentina

Congreso; XLI REUNION SAFE (SOCIEDAD ARGENTINA DE FARMACOLOGIA EXPERIMENTAL); 2009

SAFE

Acute toxic dosing models (ATD) of methamphetamine (METH) have previously shown to affect dopaminergic and/or serotonergic systems in the rodent brain. In order to explore potential neuroprotective effects of modafinil, a vigilance enhancer/antinarcoleptic drug, Swiss Webster mice were injected with a METH ATD protocol (3 X 7 mg/kg, i.p. injections, 3 hour apart), modafinil (180 mg/kg, 2 i.p. injections, 1h before first METH injection and 1h before third injection) or METH+modafinil; control group received vehicles. As expected, METH induced hyperthermia, but modafinil did not block the effect. We then measured monoamine striatal content by HPLC 6 days after METH ATD. The group that received METH showed depletion on both DA and dopaminergic metabolites; no serotonergic depletion was observed. However, the group that received the co-administration of modafinil and METH showed similar dopaminergic content values to the control (vehicle-vehicle) group suggesting a modafinil protective effect against METH-induced dopaminergic depletion. Also, we performed behavioral analysis of mice spontaneous exploratory activity and we found a subtle decrease of total locomotion and velocity in METH treated groups (6 days after last METH injection), modafinil co-administration was not able to modulate this effect. Supported by Grants from: ANPCyT PICT 2007-01009 (to Dr. Urbano), and ANPCyT PICT 2005-31953 and UBACYT M073 (to Dr. Wikinski).