Modafinil treatment counteracts methamphetamine-induced glial activation in mice striatal tissue

MARIANA RAINERI; BETINA GONZALEZ; BELEN GOITIA; VIVIANA PESKIN; EDGAR GARCIA-RILL; FRANCISCO URBANO; VERONICA BISAGNO

New Orleans

Congreso; Neuroscience 2012, SfN's 42nd annual meeting; 2012

Society for Neurosciences

Modafinil (MOD) is a stimulant drug used as a cognitive enhancer and it is alsoprescribed to treat psychostimulant addiction. Methamphetamine (METH)intake produces deleterious effects in brain areas including striatal toxicity andactivation of glial cells. In order to determine if pre-treatment with MOD couldcounteract METH-induced glial activation in striatal tissue, female C57BL/6mice 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 METHinjections). After 48hs, METH treated group exhibited striatal reactivemicrogliosis (measured by ILB4 immunostaining) and astrogliosis (measured byGFAP immunostaining). Tyrosine hydroxylase (TH) and dopamine transporter(DAT) immunostaining were not different than vehicle treated animals levels.METH+MOD treated animals showed glial activation values and TH and DATlevels that were similar to those found in vehicle groups (p<0.001). MOD itselfdid not significantly increased glial response or altered TH and DAT levels. Sixdays after treatment, striatal astrogliosis was still present in METH treatedanimals without signs of microgliosis (p<0.001) along with decreased TH andDAT levels (p<0.05). MOD+METH group showed some degree of activatedastroglia but no signs of microgliosis or altered levels of TH and DAT (p<0.05).MOD itself did not significantly modifiy any of these variables. Our resultssuggest that MOD managed to counteract microglial and astroglial activationinduced by METH by an early intervention in the temporal onset ofMETH-induced dopamine toxicity.