Melatonin's gastroprotective and antistress roles involve both central andperipheral effects

Systemic administration of melatonin (5 to 20 mg/kg) has been reported to i nhibit the induction of acute gastric mucosal lesions by stress or ischemia -reperfusion in rats. We recently demonstrated that intracisternal (i.c.) m elatonin at low doses (1 to 100ng) dose-dependently decreased acid and peps in outputs in rats. The aim of the present study was to further investigate the peripheral and central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay, we measured melatonin concentrations in the plasm a and cerebrospinal fluid (CSF) of the cisterna magna in rats subjected to water immersion restraint stress and given intraperitoneal (i.p.) or i.c, i njection of melatonin. Water immersion restraint stress was followed by a s ignificant duration-related increase in peripheral plasma melatonin levels; the stress similarly produced a time-dependent increase in the extent of g astric mucosal lesions. Administration of melatonin (1 or 10 mg/kg, i.p., o r 100 ng/10 mul, i.c.) significantly reduced the extent of stress-induced g astric damage, by 46%, 67%, and 54%, respectively. The effective i.c. dose of melatonin was at least 10000-fold smaller than the effective i.p. dose. Melatonin levels in plasma and CSF after the i.p, injection of melatonin at 10 mg/kg were dramatically higher than those after the i.c. injection of v ehicle or 100 ng of melatonin. Our results suggest that the peripheral gast roprotective action of melatonin should be investigated with due regard to these central effects.