Neuroprotective properties of modafinil on methamphetamine-induced glial activation in mouse striatum

MARIANA RAINERI; BELÉN GOITIA; VIVIANA PESKIN; EDGAR GARCIA-RILL; FRANCISCO J. URBANO; VERÓNICA BISAGNO

Huerta Grande

Congreso; XXVI Congreso Anual SAN; 2011

Sociedad Argentina de Investigación en Neurociencias

Modafinil (MOD) is a stimulant used as a cognitive enhancer and is also prescribed to treat psychostimulant addiction. Methamphetamine (METH) intake produces deleterious effects in brain areas. In order to determine if MOD was able to counteract METH-induced glial activation, mice were treated with a METH “binge” protocol (4x5mg/kg, i.p., 2h apart) co-administrated with MOD (2x90mg/kg, i.p., 1h before 1st and 4th METH injections). After two days, METH treated group exhibited striatal reactive microgliosis and enhanced GFAP immunostaining but normal levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT). When METH was co-administered with MOD, glial activation values and TH and DAT levels were similar to those found in saline/MOD groups (p<0.001). Six days after treatment, astrogliosis was still present in METH treated animals without signs of microgliosis (p<0.001) along with diminished TH and DAT levels (p<0.05). In MOD+METH group less activated astroglia and no signs of microgliosis or altered levels of TH and DAT were found (p<0,05). Our results suggest that MOD managed to block glial activation by an early intervention in the temporal onset of METH-induced dopamine terminal toxicity. Grants: PICT 2007-1009/2008-2019, PIDRI-PRH 2007, PIP 11420100100072.