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Ghrelin (Gr) is an orexigenic peptide that acts via its specific receptor, GHSR-1a distributed throughout the brain, being mainly enriched in pituitary, cortex and hippocampus (Hp) modulating a variety of brain functions. Behavioral, electrophysiological and biochemical evidence indicated that Gr modulates the excitability and the synaptic plasticity in Hp. The present experiments were designed in order to extend the knowledge about the Gr effect upon structural synaptic plasticity since morphological and quantitative changes in spine density after Gr administration were analyzed "in vitro" and "in vivo". The results show that Gr administered to hippocampal cultures or stereotactically injected in vivo to Thy-1 mice increases the density of dendritic spines (DS) being the mushroom type highly increased in secondary and tertiary extensions. Spines classified as thin type were increased particularly in primary extensions. Furthermore, we show that Gr enhances selectively the expression of BDNF-mRNA species.