Evaluation of the gastric mucosal effects of different antidepressant drugs in the rat

ABSTRACT

Investigations were performed in the rat to evaluate the effects of different classes of antidepressant drugs on the gastric mucosal damage evoked by indomethacin and on gastric acid secretion. Following pylorus-ligation, indomethacin [20 mg/kg] was given subcutaneously and rats received 2 ml of 0.15 N HCI into their stomachs. Immediately afterwards, the drugs under study were given by the subctaneous route. Rats were killed 4 h after pylorus-ligation, and the number of gastric mucosal lesions were noted, their severity calculated and gastric acid secretory responses determined. The selective 5-hydroxytryptamine [serotonin] reuptake inhibitors [SSRIs] fluoxetine and sertraline caused dose-related increase in the degree of gastric mucosal injury caused by indomethacin. Similar effects were seen on administration of the heterocyclic agent; trazodone. In contrast, the indomethacin-induced lesion scores were remarkably reduced in rats treated with the non-selective noradrenaline and, serotonin reuptake inhibitors; imipramine and amitriptyline. Gastric acid secretion was increased by fluoxetine and sertraline administration, but reduced in rats treated with imipramine or amitriptyline. It is concluded that in the rat, the SSRIs fluoxetine and sertraline and the atypical antidepressant, trazodone, potentiate gastric mucosal damage caused by indomethacin in the presence of acid in the stomach. These results also suggest that changes in gastric acid secretion are involved in the modulatory effects induced by antidepressant drugs on gastric mucosal injury