RAPID COMMUNICATION Role of Platelet-Activating Factor in Long-Term Potentiation of the Rat Medial Vestibular Nuclei

Grassi, Silvarosa, Ermelinda Francescangeli, Gianfrancesco anism, as mGluRs are greatly implied in increasing the glutaGoracci, and Vito E. Pettorossi. Role of platelet-activating factor mate release (Pin and Duvoisin 1995). The possible exisin long-term potentiation of the rat medial vestibular nuclei. J. tence of presynaptic mechanisms at vestibular level leads us Neurophysiol. 79: 3266–3271, 1998. In rat brain stem slices, we to ascertain whether mediators, which are reported to play a investigated the role of platelet activating factor (PAF) in longrole in coupling the postsynaptic and presynaptic phenomena term potentiation (LTP) induced in the ventral part of the medial (Davis and Murphey 1994; Medina and Izquierdo 1995; vestibular nuclei (MVN) by high-frequency stimulation (HFS) of Williams et al. 1993), are involved in the vestibular LTP. the primary vestibular afferent. The synaptosomal PAF receptor In particular, it has been demonstrated that platelet activatantagonist, BN-52021 was administered before and after HFS. BNing factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phospho52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, choline) , is involved in the induction of LTP in the hippowhich completely developed after the drug wash-out. The same campus as a retrograde messenger, which mediates the glutaeffect was obtained by using CV-62091, a more potent PAF antagomate increase accompanying LTP (Clark et al. 1992; Kato nist at microsomal binding sites, but with concentrations higher et al. 1994; Kornecki et al. 1996; Wierasko et al. 1993). than those of BN-52021. By contrast both BN-52021 and CV-6209 In fact, PAF receptor antagonist, BN-52021, prevents LTP had no effect on the potentiation once induced. This demonstrates induction (Arai and Lynch 1992; Kato et al. 1994) and that PAF is involved in the induction but not in the maintenance application of carbamyl-PAF (c-PAF), a nonhydrolyzable of vestibular long-term effect through activation of synaptosomal PAF analogue, induces LTP (Izquierdo et al. 1995; Kato PAF receptors. In addition, we analyzed the effect of the PAF et al. 1994; Packard et al. 1996; Wierasko et al. 1993). analogue, 1-O-hexadecyl-2-O-(methylcarbamyl)-sn-glycero-3Furthermore, BN-52021 has been reported recently to affect phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-Ohexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular the firing rate of MVN neurons (Maclennan et al. 1996), responses. Our results show that MC-PAF, but not Lyso-PAF insuggesting the existence of PAF receptors at this level. duced potentiation. This potentiation was prevented by D,L-2In the present study, we investigated whether PAF might amino 5-phosphonopentanoic acid, suggesting an involvement of play a role in vestibular LTP. Toward this aim we analyzed N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and the effect of PAF receptor blockade on the induction and CV-6209, the MC-PAF potentiation was reduced or abolished. The maintenance of HFS-LTP and the possibility of inducing dose-effect curve of MC-PAF showed a shift to the right greater LTP by exogenous PAF administration. under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal