Avaliação da contração da musculatura lisa do trato gastrointestinal e geniturinário em um modelo animal de depressão

Abstract

Several reports have demonstrated that depressive disorder is strongly related to somatic symptoms mainly characterized by gastrointestinal (constipation, delayed gastric emptying etc) or genitourinary (incontinence, overactive bladder, delayed ejaculation, poor sperm quality etc) alterations. The pathophysiological mechanisms behind the relationship between depressive disorder and somatic symptoms are still not fully understood. Therefore, this study aimed to evaluate the motor activity of gastrointestinal (fundus of stomach and duodenum) and genitourinary tract (bladder). Adult male mice were submitted to learned helplessness model (being classified as helpless and resilient) or controllable stress. After that, animals were euthanized and the fundus of stomach, duodenum or bladder isolated and mounted in a standard organ bath preparation. We evaluated the contractile effects induced by KCl 80 mM for 5 min or carbachol (muscarinic agonists; 10-7 – 10-3M). The relaxant effect of isoproterenol (β adrenoceptor agonist; 10-10 – 10-4M) was checked. Animals from different experimental group were also used for analyzing of gastric emptying and intestinal transit. We found an increase of the KCl induced contractions by about 120% in bladder from resilient animals. The maximum effect of carbachol was augmented (~95%) in bladder from helpless and resilient animals when compared to control. We also found that the potency of carbachol was 3-fold higher in bladder from resilient mice compared to control. The relaxing induced effects of isoproterenol were decreased by 30% in bladder from both helpless and resilient mice. The maximum effect of carbachol was increased by 50% and 30% in fundus of stomach from helpless and resilient mice, respectively. On the other hand, the maximum relaxing effects promoted by isoproterenol were reduced by 20% in fundus of stomach from resilient mice when compared to control. Duodenum contractions induced by KCl or carbachol were not altered in helpless or resilient mice although the maximum effect of isoproterenol was diminished by 30% in resilient mice. The controllable stress did not alter the response of bladder, fundus of stomach or duodenum to KCl, carbachol or isoproterenol. Further, animals submitted to learned helplessness or controllable stress did not exhibited alterations in gastric emptying or intestinal transit. In conclusion, incontrollable stress and not depressive phenotype (helpless animals) or controllable stress could be related to the alterations in motor activity of bladder and fundus of stomach. More studies are needed to identify the molecular mechanism by which stress might affect the motor activity of gastrointestinal or genitourinary tract.