Modafinil attenuates methamphetamine acute toxic effects in mice

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

Huerta Grande, Cordoba, Argentina

Congreso; IIRCN- Second Joint Meeting of the Argentine Society for Neuroscience (SAN: XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias) and the Argentine Workshop in Neuroscience (TAN: XII Taller Argentino de Neurociencias).; 2010

SAN-TAN

Long term Methamphetamine (METH) exposure has been shown to produce deleterious effects on brain function. Recent clinical data have supported the use off-label of Modafinil (MOD) for the treatment of psychostimulant addiction. Here we evaluate the potential neuroprotective role of MOD on METH neurotoxic effects in mice treated either with a single injection (2 or 7 mg/kg) or with a binge dosing protocol of METH (3x 7mg/Kg, ip. 3 h apart) co-administrated with MOD (2x 180 or 90 mg/Kg, 1 h before first and third METH injection); control groups received vehicles. As expected, acute METH administration induced hyperlocomotion and increased continuous sniffing compared to MOD and control group; MOD induced a dose dependent increase in locomotor activity without altering stereotyped behavior; MOD+METH group exhibited locomotor activity values similar to the saline group but showed enhanced stereotyped behavior. Six days after METH binge, reduced distance traveled was observed in METH treated animals, except for the group pretreated with MOD 90 mg/kg. Striatal dopamine content (measured by HPLC) and TH immunoreactivity decreased in METH group while MOD+METH showed similar values compared to the saline group. Our results suggest a possible protective role of MOD against METH acute toxicity. Supported by: PICT 2007-1009 (F.U.), PICT 31953, UBACyT M013 (S.W.)