RT info:eu-repo/semantics/article T1 Activity of the hippocampal somatostatinergic system following daily administration of melatonin A1 Izquierdo Claros, Rosa María A1 Boyano Adánez, María del Carmen A1 Arilla Ferreiro, Eduardo K1 Somatostatin receptors K1 Melatonin K1 Adenylyl cyclase K1 G proteins K1 Hippocampus K1 Rat K1 Bioquímica K1 Biochemistry K1 Science K1 Ciencia AB If melatonin or its analogs are to be used therapeutically in humans, their chronic effects on responsiveness of melatonin target cells need to be assessed. We have previously demonstrated that acute melatonin treatment regulates the somatostatinergic system in the rat hippocampus. In the present study, we have investigated the effects of subchronic and chronic daily treatment with melatonin on the somatostatinergic system in the rat hippocampus. Male Wistar rats (200-250 g) were injected with melatonin (25 ¿g/kg body weight, subcutaneously) daily for 4, 7 or 14 days and sacrificed 24 h after the last injection. Melatonin administration for 4 days induced a decrease in the hippocampal somatostatin (SRIF)-like immunoreactivity content as well as a decrease in the number of SRIF receptors and an increase in their apparent affinity. The decreased number of SRIF receptors in the melatonin (4 days)-treated rats was associated with a decreased capacity of SRIF to inhibit both basal and forskolin-stimulated adenylyl cyclase activity. These melatonin-induced effects reversed to control values after 7 or 14 days of treatment. Hippocampal membranes from control and melatonin-treated rats showed similar Gi and Gs activities. Melatonin treatment altered neither the functional Gi activity nor the Gi¿1 or Gi¿2 levels at any of the time periods studied. The present results suggest that chronic exposure to melatonin results in a tolerance of the hippocampus to this hormone. PB Elsevier SN 0169-328X YR 2004 FD 2004 LK http://hdl.handle.net/10017/2259 UL http://hdl.handle.net/10017/2259 LA eng DS MINDS@UW RD 02-jun-2023