Premium
Morphine withdrawal in cortical slices: suppression by Ca 2+ ‐channel inhibitors of abstinence‐induced [ 3 H]‐noradrenaline release
Author(s) -
PellegriniGiampietro Domenico E.,
Bacciottini Lucia,
Carlà Vincenzo,
Moroni Flavio
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb10308.x
Subject(s) - nimodipine , (+) naloxone , dihydropyridine , morphine , chemistry , long term potentiation , depolarization , pharmacology , endocrinology , antagonist , calcium , medicine , receptor , biochemistry , organic chemistry
1 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. 2 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. 3 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. 4 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. 5 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.