AN ANTICATALASE LENTIVIRAL VECTOR REDUCED ETHANOL INTAKE IN DEVELOPMENTALLY-LEAD-EXPOSED RATS

MATTALLONI MS; SALINAS C; QUINTANILLA ME; HERRERA-MARSCHITZ M; ISRAEL Y; CANCELA LM; RIVERA-MEZA; VIRGOLINI MB

Valencia

Congreso; 15TH ESBRA CONGRESS; 2015

Previous reports indicate that developmentally-lead (Pb)-exposed rats consumed more ethanol than theircontrol counterparts. Based on pharmacological and biochemical evidences, we attribute these differencesto catalase (CAT), the main enzyme involved in brain ethanol oxidation to acetaldehyde, a key componentin ethanol´s positive reinforcing effects. Thus, in the present study we sought to prevent brain CATexpression by the microinfusion of an antiCAT lentiviral vector in the ventral tegmental area (VTA) in orderto evaluate its impact on voluntary ethanol intake in control and Pb-exposed animals. To this end, apshRNA antiCAT vector was generated, packed in HEK 293T cells, and titrated by quantitative PCR.Thirty-five-day-old male Wistar rats perinatally exposed to 220 ppm Pb or vehicle with 2 h/day access towater or increasing concentrations of ethanol (2-10% v/v) were microinfused with the lentiviral vector atthe beginning (day 1) or at the end (day 20) of the experiment. Ethanol intake was registered for severaladditional days, and rats sacrificed thereafter for VTA dissection to measure CAT expression. Thelentiviral administration prior to the ethanol intake scheme prevented the emergence, while itsadministration later in the test reversed the elevated ethanol intake reported in the Pb-exposed group.Overall, by using a genetic approach, these results point out a key role for CAT in the elevated ethanolintake reported in perinatally Pb-exposed animals, and resemble data obtained with pharmacologicalmanipulations.Financial support: FonCyT, SeCyT and CONICET (MBV); FONDECYT 11130241 (MRM); BNI P09-015-F(MHM).