Morphine withdrawal in cortical slices: suppression by Ca2+-channel inhibitors of abstinence-induced [3H]-noradrenaline release

Br J Pharmacol. 1988 Mar;93(3):535-40. doi: 10.1111/j.1476-5381.1988.tb10308.x.

Abstract

1. The effects of morphine withdrawal were evaluated in vitro by monitoring the actions of naloxone on the depolarization-induced release of [3H]-noradrenaline (NA) in cortical slices taken from naïve or dependent rats. The effects of dihydropyridine molecules acting on Ca2+-channels (nimodipine and Bay K 8644) were also studied in this model. 2. Naloxone (10(-8)-10(-5) M) dose-dependently enhanced the K+ induced release of [3H]-NA in slices taken from dependent rats, but failed to modify the [3H]-NA release from 'naïve' slices. 3. The naloxone-induced potentiation of release was significantly reversed by nimodipine (10(-8)-10(-6) M). These doses of nimodipine did not change [3H]-NA release (both basal and K+ induced) in preparations obtained from naïve rats. 4. Bay K 8644 potentiated the K+-induced [3H]-NA release from cortical slices taken from naïve rats to a similar extent as that of naloxone in dependent rats. 5. These results suggest that the naloxone potentiation of the depolarization-induced [3H]-NA release in slices taken from dependent rats may be considered a model of morphine withdrawal in vitro. In this model dihydropyridine Ca2+-channel antagonists suppress morphine-withdrawal effects in a similar manner to observations made in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Calcium / metabolism*
  • Cerebral Cortex / metabolism*
  • Dihydropyridines / pharmacology
  • Disease Models, Animal
  • In Vitro Techniques
  • Ion Channels / drug effects*
  • Morphine / adverse effects*
  • Naloxone / pharmacology
  • Nimodipine / pharmacology
  • Norepinephrine / metabolism*
  • Rats
  • Substance Withdrawal Syndrome / metabolism*
  • Tritium

Substances

  • Dihydropyridines
  • Ion Channels
  • Tritium
  • Naloxone
  • Nimodipine
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Morphine
  • 1,4-dihydropyridine
  • Calcium
  • Norepinephrine