Leptin-induced downregulation of the rat hippocampal somatostatinergic system may potentiate its anorexigenic effects

► Food restriction augments somatostatin receptor density in a CREB-mediated mechanism. ► Increased hippocampal somatostatinergic tone has orexigenic effects. ► Downregulation of somatostatinergic system potentiates leptin effects. ► Leptin modifies the concentrations of molecules involved in cAMP regulation. ► Leptin antagonist normalizes abnormal somatostatin signaling induced by leptin.