New neuroprotective role of modafinil against methamphetamine acute toxic effects in mice

MARIANA RAINERI; BELÉN GOITIA; IRENE R. E. TARAVINI; VIVIANA PESKIN; SERGIO GIORGERI; FRANCISCO J. URBANO; VERÓNICA BISAGNO

Washington, DC

Congreso; 41st Meeting of the Society for Neuroscience; 2011

Society for Neuroscience

Modafinil (MOD) is an antinarcoleptic drug that is also being used off-label to treat psychostimulant addiction. Methamphetamine (METH) intake produces deleterious effects on brain function. The objective of the present study was to explore the neuroprotective role of MOD on METH neurotoxic effects. Mice were treated either with a METH single i.p. injection (2 or 7 mg/kg) or with a binge dosing protocol of METH (3 i.p. injections of 7mg/kg, 3 h apart) co-administrated with MOD (2 injections of 180 or 2 injections of 90 mg/kg, i.p., 1 h before first and third METH injection). Acute METH (7mg/kg) administration induced hyperlocomotion (p<0.0001, ANOVA) and increased continuous sniffing compared to MOD and saline/vehicle values (p<0.05, ANOVA). Acute MOD increased locomotor activity in a dose dependent manner (p<0.0001, ANOVA) without enhancing stereotyped behavior. Groups receiving the combination of MOD and METH exhibited locomotor activity values similar to those of saline/vehicle groups and enhanced stereotyped behavior (i.e., increased time spent in continuous sniffing), (p<0.05, ANOVA). Six days after METH binge, spontaneous locomotor activity was recorded and reduced distance traveled was observed in METH treated animals (p<0.0001, ANOVA). MOD pre-treatment was not able to counteract this effect. Striatal dopamine, HVA, DOPAC content (measured by HPLC) and TH immunoreactivity were decreased in METH treated animals (p<0.01, ANOVA) while MOD+METH groups showed similar values compared to saline/vehicle groups (measured 6 days after last METH injection). Our results suggest a possible protective role of MOD against METH acute toxicity.