P117.-Methamphetamine and modafinil differentially alter mRNA expression of epigenetic regulators in the mouse prefrontal cortex

GONZALEZ B; MUÑIZ JA; CADET JL; GARCIA-RILL E; URBANO FJ; BISAGNO V

HUERTA GRANDE, CORDOBA ARGENTINA

Congreso; XXIX ANNUAL MEETING AND SAN-ISN SMALL COFERENCE AND COURSE; 2014

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS

Chronic methamphetamine (METH) leads to long-lasting cognitive dysfunction in humans and animal models. Modafinil (MOD) is a wake-promoting compound that is being prescribed off label for the treatment of METH dependence. We previously demonstrated that modafinil can rescue METH-induced deficits on memory retention through a mechanism that involves restoration of ERK signaling in the mPFC. In this study, we used cPCR to measure mPFC epigenetic regulators mRNA, include HATs, HDACs, DNMTs, and TETs. We also quantified c-Fos expression as a marker of neuronal activation. METH (1 mg/kg sc) was administered as a single dose or repeatedly for 7 days and we evaluated the effects of a single dose of MOD (90 mg/kg ip) given alone or after METH (METH-MOD). Tissues were collected 1 hr after administration. We found that single dose and repeated METH treatments caused increased expression of Tet1 mRNA and decreased Hdac1, Hdac2, Hat1, and Dnmt3A. METH withdrawal also showed decreased expression of Hdac1 and Hdac2. MOD showed decreased Hdac2 and increased c-Fos expression. The METH-MOD group showed a differential expression pattern when compared with METH and MOD alone: decreased Tet2, Hdac1 and Hdac2 mRNA levels to lower values than METH. Our results show that METH and MOD exert differential effects on epigenetic marker expression in the mPFC, with METH altering a larger set than MOD. These differences could be related to the METH-induced cognitive impairments and mPFC abnormalities.