ANTISENSE OLIGONUCLEOTIDE TO C-FOS BLOCKS THE ABILITY OF ARGININE-VASOPRESSIN TO MAINTAIN ETHANOL TOLERANCE

Administration of the neuropeptide, arginine vasopressin, can reduce t he rate of dissipation of functional ethanol tolerance in mice that ha ve acquired that tolerance. We previously showed that intracerebrovent ricular vasopressin administration can also produce an increase in sep tal c-fos mRNA levels. To evaluate the role of the increased expressio n of c-fos in the ability of vasopressin to maintain tolerance, ethano l-tolerant mice were given intracerebroventricular injections of vasop ressin in the presence or absence of an antisense oligonucleotide to c -Jos. The antisense oligonucleotide completely blocked the ability of vasopressin to maintain ethanol tolerance, while a missense oligonucle otide was without effect. The antisense oligonucleotide also attenuate d the increase in septal c-fos mRNA levels caused by vasopressin. The results provide evidence for a role of c-fos expression in the mainten ance of ethanol tolerance by vasopressin.