INTERACTIONS BETWEEN DIFFERENT ANTIDEPRESSANTS AND MORPHINE ALTER GASTROINTESTINAL TRANSIT IN MICE

To determine different serotoninergic antidepressants' effects on the gastrointestinal (GI) inhibiting effect induced by morphine, mice were pretreated with mianserin (a tetracyclic antidepressant with multiple 5-HT receptor subtypes interactions) and with fluoxetine (a selective 5-HT reuptake inhibitor). Mianserin alone, produced gastrointestinal inhibition in a dose-dependent manner. Naloxone did not reverse this i nhibiting effect, indicating that different mechanism of action are in volved in morphine- and mianserin-induced inhibition of the gastrointe stinal transit. Fluoxetine injected alone produced an increased propul sive motility of the GI transit. This effect was not reversed by nalox one. Fluoxetine did not reduce significantly mianserin-induced inhibit ion of GI transit. Fluoxetine also mildly reversed morphine-induced ga strointestinal inhibition, suggesting some degree of involvement of th e opiates through the serotoninergic system. (C) 1997 Elsevier Science Inc.