Activation of gonadotropin-releasing hormone receptors induces a long-term enhancement of excitatory postsynaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus.

Whole-cell patch-clamp recordings were made from CA1 pyramidal neurons of the rat hippocampus to study the modulation of gonadotropin-releasing hormone (GnRH) on synaptic transmission mediated by ionotropic glutamate receptors. Leuprolide (10(-9)-10(-7) M), a specific GnRH analog, concentration-dependently elicited a long-lasting potentiation of excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors. GnRH receptor-induced synaptic potentiation was blocked by 1 microM [Acetyl-3,4-dehydro-Pro1,D-p-F-Phe2,D-Trp3,6]-LHRH, a specific GnRH receptor antagonist. Furthermore, GnRH receptor-induced synaptic potentiation was associated with the stimulation of protein kinase C (PKC), being considerably attenuated by a potent PKC inhibitor (30 microM H-7). The results suggest a long-term enhanced modulation of GnRH on synaptic transmission mediated by ionotropic glutamate receptors, possibly via the actions of PKC in the hippocampus that is an important integrative system in the regulation of reproductive processes.