title: Effect of potassium channel modulators on morphine withdrawal in mice.
abstract: The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K(+) (ATP)) channel modulators were injected intraperitoneally (i.p.) 30 minutes before the naloxone. It was found that a K(+) (ATP) channel opener, minoxidil (12.5-50 mg/kg i.p.), suppressed the morphine withdrawal significantly. On the other hand, the K(+) (ATP) channel blocker glibenclamide (12.5-50 mg/kg i.p.) caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K(+) (ATP) channels play an important role in the genesis of morphine withdrawal and K(+) (ATP) channel openers could be useful in the management of opioid withdrawal. As morphine opens K(+) (ATP) channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K(+) currents.
authors.affiliation: Pharmacology Department, Mahatma Gandhi Medical College, Jaipur, Rajasthan, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Seth
authors.forename: Mushtaq
authors.initials: M
authors.lastname: Ahmad
authors.forename: Prerna
authors.initials: P
authors.lastname: Upadhyaya
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.forename: Vijay
authors.initials: V
authors.lastname: Moghe