Attenuated methamphetamine induced neurotoxicity by modafinil administration in mice.

RAINERI M; PESKIN V; GOITIA B; TARAVINI IR; GIORGERI S; URBANO FJ; BISAGNO V

SYNAPSE

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2011 vol. 65 p. 1087 - 1098

0887-4476

Methamphetamine (METH) is a highly addictive drug that mightinduce neurotoxicity. Clinical trials have reported that modafinil, a wake-promotingagent used to treat sleep disorders, may have some efficacy for the treatment of psychostimulantaddiction. In this study we tested possible neuroprotective effects ofmodafinil after toxic METH administration in mice. We evaluated the effect of modafinil(two injections of either 90 or 180 mg/kg) and METH binge (3 3 7 mg/kg i.p. injections,3-h apart) coadministration on DA striatal content, TH immunoreactivity instriatal areas and spontaneous locomotor activity. We also investigated acute locomotoractivity and stereotypy profile in mice treated with a single METH dose (2 and 7mg/kg) pretreated with modafinil (90 and 180 mg/kg). We found that mice treatedwith a METH binge showed a marked decrease in DA and dopaminergic metabolitesas well as lower levels of TH immunoreactivity in the dorsal striatum. Pretreatmentwith modafinil (both 90 and 180 mg/kg) attenuated these effects but did not preventMETH induced decrease in locomotion. We also found that groups that received thecombination of both modafinil and single dose METH showed a decrease in total distancetraveled in an open field compared with METH groups. We observed an incrementin the time mice expended doing stereotypic movements (continuous sniffing) inthe group that received the combination of both METH and modafinil (i.e., decreasinglocomotion). Our results suggest a possible protective role of modafinil against METHacute striatal toxicity.