The effect of nimodipine on memory impairment during spontaneous morphine withdrawal in mice: Corticosterone interaction

Eur J Pharmacol. 2012 Nov 15;695(1-3):83-7. doi: 10.1016/j.ejphar.2012.08.022. Epub 2012 Sep 7.

Abstract

Effects of the nimodipine, L-type calcium channel antagonist, has been studied on memory loss caused by spontaneous morphine withdrawal in mice. Mice were made dependent by increasing doses of morphine over three days. Memory was evaluated using object recognition task, which is based on tendency of rodents to exploration of new objects. The test was comprised of three sections: 15 min habitation, 12 min first trial and 5 min test trial. Recognition index was evaluated 4h after the last dose of morphine. Nimodipine was administrated either in chronic form (1, 5 and 10mg/kg) with daily doses of morphine or it was given as a single injection (5 and 10mg/kg) on the last day. Nimodipine in both treatment forms prevented the memory impairment following spontaneous morphine withdrawal. Corticosterone concentration was increased in brain and blood of mice during abstinence phase and pretreatment with nimodipine prevented the increase in brain and blood corticosterone concentration. The results show that blockade of L-type calcium channels improves memory deficits caused by morphine withdrawal. This indicates that some kind of treatments, such as nimodipine, administrated over the acute withdrawal phase, can prevent memory deficit during withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Corticosterone / blood
  • Corticosterone / metabolism*
  • Male
  • Memory Disorders / blood
  • Memory Disorders / complications
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism*
  • Mice
  • Morphine / pharmacology*
  • Nimodipine / pharmacology*
  • Nimodipine / therapeutic use
  • Substance Withdrawal Syndrome / complications*

Substances

  • Calcium Channel Blockers
  • Nimodipine
  • Morphine
  • Corticosterone