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 inhibiting effect, indicating that different mechanism of action are involved in morphine- and mianserin-induced inhibition of the gastrointestinal transit. Fluoxetine injected alone produced an increased propulsive motility of the GI transit. This effect was not reversed by naloxone. Fluoxetine did not reduce significantly mianserin-induced inhibition of GI transit. Fluoxetine also mildly reversed morphine-induced gastrointestinal inhibition, suggesting some degree of involvement of the opiates through the serotoninergic system.