Involvement of PKA and ERK pathways in ghrelin‐induced long‐lasting potentiation of excitatory synaptic transmission in the CA 1 area of rat hippocampus

Acute effects of ghrelin on excitatory synaptic transmission were evaluated on hippocampal CA 1 synapses. Ghrelin triggered an enduring enhancement of synaptic transmission independently of NMDA receptor activation and probably via postsynaptic modifications. This ghrelin‐mediated potentiation resulted from the activation of GHS ‐R1a receptors as it was mimicked by the selective agonist JMV 1843 and blocked by the selective antagonist JMV 2959. This potentiation also required the activation of PKA and ERK pathways to occur as it was inhibited by KT 5720 and U0126, respectively. Moreover it most probably involved Ca 2+ influxes as both ghrelin and JMV 1843 elicited intracellular Ca 2+ increases, which were dependent on the presence of extracellular Ca 2+ and mediated by L‐type Ca 2+ channels opening. In addition, ghrelin potentiated AMPA receptor‐mediated [Ca 2+ ]i increases while decreasing NMDA receptor‐mediated ones. Thus the potentiation of synaptic transmission by GHS ‐R1a at hippocampal CA 1 excitatory synapses probably results from postsynaptic mechanisms involving PKA and ERK activation, which are producing long‐lasting enhancement of AMPA receptor‐mediated responses.