682 a new experimental model for HIV 1 lesions in the brain based on SV40 vectors expressing envelope glycoprotein gp120

682 A New Experimental Model for HIV 1 Lesions in the Brain Based on SV40 Vectors Expressing Envelope Glycoprotein gp120 680 Alcohol Drinker Rats Lower Their Ethanol Intake for One Month after a Singl[.]

680 Alcohol Drinker Rats Lower Their Ethanol Intake for One Month after a Single Injection of an Adenoviral Vector Carrying an Antisense Gene for Aldehyde Dehydrogenase Paula Ocaranza,' Maria Elena Quintanilla.? Lutske Tampier,' Eduardo Karahanian,' Amalia Sapag ,' Yedy lsrael.P:' 'Gene Pharmacotherapy Laboratory Department 0/Pharmacological and Toxicological Chemistry Faculty ofChemical and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile; 2Program 0/ Molecular and Clinical Pharmacology, Faculty 0/ Medicine, Universidad de Chile, Santiago, Chile; "Faculty 0/ Health Sciences, Universidad Diego Portales, Santiago, Chile; "Department 0/Pathology, Anatomy and Cell Biology, Thomas Jefferson University; Philadelphia, PA Nature has developed a proteetive mechanism against alcohol abuse and alcoholism In most individuals aldehyde dehydrogenase2 (ALDH2) readily oxidizes acetaldehyde, a product of ethanol metabolism, allowing excessive alcohol consumption In contrast, subjects who carry a point mutation in the ALDH2 gene which lowers aldehyde dehydrogenase activity are strongly protected against alcohol abuse and alcoholism by 66 % to 100 % because of the aversion triggered by the elevation of blood acetaldehyde upon alcohol drinking The aim of this study was to mimic such an aversion to ethanol in rats by inhibiting the expression of the Aldh? gene Rats bred as heavy alcohol drinkers (UChB) from the Wistar strain were allowed free access to both 10 % ethanol (v/v) and water for 45-60 days (ethanol intake 6-7 g/kg/day) After this time animals were administered, by a single tail vein injection, an adenovirus (lx10 12 particles per kg) carrying an antisense gene for the entire Aldh2 mRNA under the control of a CMV promoter and were subsequently deprived of ethanol for days Afer the withdrawal period animals were allowed access to both 10 % ethanol and water for one hour each day On the first day of re-access to ethanol both the control and the antisense treated animals consumed equal amounts ofethanol (1-1.2 g/kg/hour), Aversion to ethanol was markedly evident on subsequent days after the animals had experienced the effects ofthe antisense RNA, with an overall reduction in alcohol intake of 50 % for 34 days (ANOVA p