Modafinil treatment prevents methamphetamine-triggered effects on pro-apoptotic BAX and anti-apoptotic Bcl-2 protein expression in mice striatum (Neurochemistry and Neuropharmacology Poster Number 165 / Session I)

B. GONZALEZ; M. RAINERI; E. GARCIA-RILL; I. N. KRASNOVA; J. L. CADET; F. J. URBANO; V. BISAGNO

Huerta Grande, Cordoba

Congreso; XXVII Congreso SAN 2012; 2012

Sociedad Argentina de Investigacion en Neurociencias (SAN)

Methamphetamine (METH) intake can cause neurotoxic damage in human users and animals. METH toxic effects include terminal degeneration and proapoptotic 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.