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

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 naive 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.

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