TY - JOUR T1 - An Antisense Oligonucleotide on the Mouse<em>Shaker</em>-like Potassium Channel Kv1.1 Gene Prevents Antinociception Induced by Morphine and Baclofen JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 941 LP - 949 VL - 281 IS - 2 AU - Nicoletta Galeotti AU - Carla Ghelardini AU - Laura Papucci AU - Sergio Capaccioli AU - Alessandro Quattrone AU - Alessandro Bartolini Y1 - 1997/05/01 UR - http://jpet.aspetjournals.org/content/281/2/941.abstract N2 - Inactivation of the Kv1.1 gene, which codes for a member of theShaker-like potassium channels by an antisense oligodeoxyribonucleotide (aODN), was carried out in mice. The effect of this inactivation on analgesia induced by morphine (5–9 mg kg−1 s.c.) and baclofen (2–5 mg kg−1 s.c.) was investigated in the mouse hot-plate test. Mice received a single intracerebroventricular injection of mKv1.1 aODN (0.5, 1.0, 2.0 or 3.0 nmol per injection), degenerated ODN or vehicle on days 1, 4 and 7. A dose-dependent inhibition of morphine and baclofen antinociception was observed 72 h after the last intracerebroventricular aODN injection, whereas degenerated ODN and vehicle, used as controls, did not affect morphine- and baclofen-induced antinociception. Sensitivity to both analgesic drugs returned to the normal range 7 days after the end of the aODN treatment, which indicated the absence of any irreversible damage or toxicity caused by aODN. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that a decrease in mKv1.1 mRNA levels occurred only in the aODN-treated group, being absent in all control groups. Furthermore, neither aODN, degenerated ODN nor vehicle produced any behavioral impairment of mice. These results indicate that the mKv1.1 potassium channel, whose gene expression we specifically modulated by means of the antisense ODN strategy, plays an important role in central analgesia induced by morphine and baclofen. The American Society for Pharmacology and Experimental Therapeutics ER -