Modafinil maintains protective effects on methamphetamine-induced toxicity at different ambient temperatures.

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

San Diego

Congreso; 2013 NIDA International Forum Poster Session; 2013

NIDA-NIH

Modafinil maintains protective effects on methamphetamine-induced toxicity at different ambient temperatures. V. BISAGNO(1), M. Raineri(1), B. Gonzalez(1), N. Colettis(2), E. Garcia-Rill(3), J. L. Cadet (4), F. J. Urbano (2). (1)Instituto de Investigaciones Farmacológicas, ININFA (UBA-CONICET). , Argentina; (2) Instituto de Fisiología, Biología Molecular y Neurociencias, IFIByNE (UBA-CONICET); (3) Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, UAMS, USA; (4) Molecular Neuropsychiatry Research Branch, NIH/NIDA Intramural Research Program, USA. Background: Methamphetamine (METH) is an illicit drug of abuse that can cause neuropsychiatric and neurotoxic damage in humans and animals. We have previously shown that modafinil can interfere with METH actions and counteract METH-induced hyperthermia, dopamine toxicity, and neuroinflammation in the striatum. Methods: In order to clarify if temperature regulation might have a role on modafinil neuroprotection against METH, we evaluated the effect of a toxic METH binge in female C57BL/6 mice (4×5 mg/kg, i.p.) and modafinil co-administration (2×90 mg/kg, i.p.) at two ambient temperatures: 14±1 °C and 29±1 °C. Body temperatures were recorded throughout the binge administration. Dopaminergic and inflammatory markers were measured in striatal tissue 6 days after treatments. Results: At 29°C, METH, given alone, induced hyperthermia (p