Morphine withdrawal in cortical slices: suppression by Ca 2+ ‐channel inhibitors of abstinence‐induced [ 3 H]‐noradrenaline release

• Published in: British journal of pharmacology Vol. 93; no. 3; pp. 535 - 540
• Main Authors: Pellegrini‐Giampietro, Domenico E., Bacciottini, Lucia, Carlà, Vincenzo, Moroni, Flavio
• Format: Journal Article
• Language: English
• Published: 01.03.1988
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb10308.x

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