Somatostatin and its analogs act in the brain to influence gastric acid secretion. Five different somatostatin receptor subtypes have been characterized (sst1 to sst5). We studied the influence of somatostatin (0.18-0.6 nmol/rat) and selective sst2, sst3 and sst5 receptor ligands on basal gastric acid secretion in conscious rats equipped with chronic gastric and intracerebroventricular (i.c.v.) cannulae. Somatostatin-14 (0.36 nmol/rat), the sst2, sst3 and sst5 receptor agonist, Des-AA1,2,4,5,12,13-[D-Tryp8,D-Cys14]somatostatin (SMS 201-995) (0.18-0.36 nmol/rat) and the sst5 receptor agonist, BIM-23052, (0.8-1.2 nmol/rat) injected i.c.v. inhibited gastric acid secretion. Maximal inhibition reaching 42%, 60% and 42% was induced by somatostatin-14 (0.36 nmol/rat), SMS 201-995 (0.18 nmol/rat) and BIM-23052 (0.8 nmol/rat) respectively. The sst2 receptor agonist, DC 32-87 (0.2-0.8 nmol/rat) and sst3 receptor agonist, BIM-23056 (0.2-1.2 nmol/rat), did not modify gastric acid secretion, except the sst3 receptor agonist at 0.4 nmol/rat which increased acid output at 20 min post-injection. The sst2 receptor agonists (0.4 nmol/rat) co-injected i.c.v. with a subthreshold dose of sst5 (0.4 nmol/rat) inhibited gastric acid secretion. These results show that i.c.v. injection of somatostatin-14 inhibits basal gastric acid secretion in conscious rats through an action on sst5 receptor subtype which can be potentiated by sst2 receptor subtype.