Modafinil treatment prevents methamphetamine-triggered effects on pro-apoptotic BAX and anti-apoptotic Bcl-2 protein expression in mice striatum

BETINA GONZALEZ; MARIANA RAINERI; EDGAR GARCIA-RILL; IRINA KRASNOVA; JEAN LUD CADET; FRANCISCO URBANO; VERONICA BISAGNO

Huerta Grande

Congreso; XXVII Congreso Anual de la SAN; 2012

Sociedad Argentina de Investigación en Neurociencias

Methamphetamine (METH) intake can cause neurotoxic damage in human users and animals. METH toxic effects include terminal degeneration and pro-apoptotic effects. Our group had previously demonstrated that Modafinil (MOD), a psychostimulant drug used to treat sleep disorders, could protect against METH-induced striatal toxicity. To further evaluate the role of MOD in neuroprotection, we first studied the temporal profile of METH-induced toxicity in the striatum with the Amino-Cupric-Silver technique. Female C57BL/6 mice, treated with a METH "binge" protocol (4x5mg/kg, ip, 2 hs apart), showed the highest degree of terminal degeneration at 16 and at 24 hs in comparison to vehicle-treated controls, therefore we decided to evaluate possible protective effects of MOD at 16 hs post METH. Mice were treated with the METH binge protocol, MOD (2x90mg/kg, ip), or with the combination of MOD+METH (2x90mg/kg, ip, 1h before the 1st and 4th METH injections). The protein expression of the pro-apoptotic BAX and the anti-apoptotic Bcl-2 was analyzed in mice striata. We found a significant increase in BAX and a decrease in Bcl2 expression in METH-treated mice. Neither MOD nor the MOD+METH combination groups showed significant changes in comparison to vehicle-treated subjects. These results indicate that MOD might protect against METH toxicity, at least in part, by interfering with METH-induced changes in pro- and anti-apoptotic signals.