Brain catalase levels in developmentally-lead-exposed rats administered with a pshRNA anticatalase lentiviral vector in ventral tegmental area

ALBRECHT, PA; MATTALLONI, MS; SALINAS C; QUINTANILLA ME; HERRERA MARSCHITZ M; ISRAEL Y; CANCELA L; RIVERA MEZA M; VIRGOLINI MB

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN

Brain catalase levels in developmentally-lead-exposed rats administered with a pshRNA anticatalase lentiviral vector in ventral tegmental area Paula Albrecht1, Mara S. Mattalloni1, Catalina Salinas2, María Elena Quintanilla2, Mario Herrera-Marschitz2,3, Yedy Israel2, Liliana M. Cancela1, Mario Rivera-Meza2,3 & Miriam B. Virgolini11IFEC-CONICET. Depto. de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina; 2Instituto de Ciencias Biomédicas, Facultad de Medicina,Universidad de Chile; 3BNI Millennium Scientific Initiative, Santiago, Chile.Catalase (CAT) is the main enzyme responsible for brain ethanol oxidation to acetaldehyde, a metabolite considered a key component in the drug?s motivational effects. We report here that the microinfusion of a pshRNA antiCAT lentiviral vector in the ventral tegmental area (VTA) prevented the acquisition and maintenance of the elevated ethanol intake observed in developmentally low-level lead (Pb)-exposed animals. To complement these results, the present study sought to measure VTA CAT levels by the Western-blot technique. Thirty-five-day-old male Wistar rats perinatally exposed to 220 ppm Pb or water with 2 h/day access to water or increasing concentrations of ethanol (2-10% v/v) were microinfused with the lentiviral vector at the beginning or towards the end of the free-choice scheme, and sacrificed at the end of the test. The results demonstrated that selectively in the Pb-exposed animals, ethanol intake enhanced VTA CAT expression when compared with the same animals at 35 day-old, this is before the implementation of the ethanol intake test. Interestingly, this effect was reversed by the pshRNA antiCAT lentivirus when it was administered at the end (although not at the beginning) of the choice test. These changes were absent in the control animals in close relationship with unmodified ethanol intake. Overall, VTA CAT expression plays a key role in the elevated ethanol intake reported in perinatally Pb-exposed animals.