Potentiating interactions between medullary serotonin and thyrotropin-releasing hormone-induced gastric erosions in rats.

The central interaction between 5-HT and exogenous and endogenous thyrotropin-releasing hormone (TRH)-induced gastric lesions was investigated in conscious rats. Intracisternal injection (i.c.) of the TRH analog, RX 77368, (2.5 nmol) in indomethacin (2 mg/kg, i.p.)-treated rats produced 1.4 +/- 0.1% of gastric corpus mucosal lesions which were aggravated by 30 and 208% by simultaneous i.c. injection 5-HT at 10 and 100 nmol, respectively, whereas i.v. 5-HT (100 nmol) had no effect. The 5-HT2/1c antagonist, ketanserin, given i.c. at 10 or 100 nmol reduced by 44 and 76%, respectively, cold restraint stress-induced 3.4 +/- 0.6% gastric lesions in indomethacin-pretreated rats whereas, when given i.v. (100 nmol), it was inactive. Ketanserin or 5-HT (100 nmol, i.c.) alone did not modify the gastric mucosa. The present data suggest a potentiating interaction between endogenous 5-HT and TRH which has implication in the understanding of medullary mechanisms involved in gastric lesion formation induced by cold restraint.