VIRGOLINI MIRIAM BEATRIZ
Congresos y reuniones científicas
Título:
AN ANTICATALASE LENTIVIRAL VECTOR REDUCED ETHANOL INTAKE IN DEVELOPMENTALLY-LEAD-EXPOSED RATS
Autor/es:
MATTALLONI MS; SALINAS C; QUINTANILLA ME; HERRERA-MARSCHITZ M; ISRAEL Y; CANCELA LM; RIVERA-MEZA; VIRGOLINI MB
Lugar:
Valencia
Reunión:
Congreso; 15TH ESBRA CONGRESS; 2015
Resumen:
Previous reports indicate that developmentally-lead (Pb)-exposed rats consumed more ethanol than their
control counterparts. Based on pharmacological and biochemical evidences, we attribute these differences
to catalase (CAT), the main enzyme involved in brain ethanol oxidation to acetaldehyde, a key component
in ethanol´s positive reinforcing effects. Thus, in the present study we sought to prevent brain CAT
expression by the microinfusion of an antiCAT lentiviral vector in the ventral tegmental area (VTA) in order
to evaluate its impact on voluntary ethanol intake in control and Pb-exposed animals. To this end, a
pshRNA 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 to
water or increasing concentrations of ethanol (2-10% v/v) were microinfused with the lentiviral vector at
the beginning (day 1) or at the end (day 20) of the experiment. Ethanol intake was registered for several
additional days, and rats sacrificed thereafter for VTA dissection to measure CAT expression. The
lentiviral administration prior to the ethanol intake scheme prevented the emergence, while its
administration 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 ethanol
intake reported in perinatally Pb-exposed animals, and resemble data obtained with pharmacological
manipulations.
Financial support: FonCyT, SeCyT and CONICET (MBV); FONDECYT 11130241 (MRM); BNI P09-015-F
(MHM).
control counterparts. Based on pharmacological and biochemical evidences, we attribute these differences
to catalase (CAT), the main enzyme involved in brain ethanol oxidation to acetaldehyde, a key component
in ethanol´s positive reinforcing effects. Thus, in the present study we sought to prevent brain CAT
expression by the microinfusion of an antiCAT lentiviral vector in the ventral tegmental area (VTA) in order
to evaluate its impact on voluntary ethanol intake in control and Pb-exposed animals. To this end, a
pshRNA 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 to
water or increasing concentrations of ethanol (2-10% v/v) were microinfused with the lentiviral vector at
the beginning (day 1) or at the end (day 20) of the experiment. Ethanol intake was registered for several
additional days, and rats sacrificed thereafter for VTA dissection to measure CAT expression. The
lentiviral administration prior to the ethanol intake scheme prevented the emergence, while its
administration 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 ethanol
intake reported in perinatally Pb-exposed animals, and resemble data obtained with pharmacological
manipulations.
Financial support: FonCyT, SeCyT and CONICET (MBV); FONDECYT 11130241 (MRM); BNI P09-015-F
(MHM).
