CORTICOTROPIN-RELEASING FACTOR PRODUCES A LONG-LASTING ENHANCEMENT OFSYNAPTIC EFFICACY IN THE HIPPOCAMPUS

We have previously demonstrated that intra-hippocampal injection of co rticotrophin-releasing factor improved memory retention of an inhibito ry avoidance learning in rats; while the electrophysiological effects corticotrophin-releasing factor produces on hippocampal neurons are la rgely uncharacterized. In the present study, we found that corticotrop hin-releasing factor injected into the dentate gyrus of hippocampus pr oduced a dose-dependent and long-lasting enhancement in synaptic effic acy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials, as well as the amplitude of population spike. The onset of corticotrophin-releasing factor-induced potentiation was slow. It was observed approximately 40 -60 min after corticotrophin-releasing factor administration and laste d for more than 5 h, This effect of corticotrophin-releasing factor wa s blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethyl amine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate rec eptor antagonist MK-801, Further, pretreatment with corticotrophin-rel easing factor receptor antagonist dose-dependently diminished tetaniza tion-induced long-term potentiation, and corticotrophin-releasing fact or and tetanic stimuli had an additive effect on hippocampal neuron ex citation. Moreover, direct injection of corticotrophin-releasing facto r increased cAMP level in the dentate gyrus, These results together su ggest that corticotrophin-releasing factor-induced potentiation simula tes the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, cortic otrophin-releasing factor-induced potentiation and long-term potentiat ion may share some similar mechanisms, and corticotrophin-releasing fa ctor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotrophin-releasing factor may play an import ant role in modulating synaptic plasticity in the hippocampus.