Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei

In rat brainstem slices, we investigated the differential role of nitric ox ide (NO) and platelet-activating factor (PAF) in long-term potentiation (LT P) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The N O scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazo-line- 1-oxyl-3-o xide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect o f carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only re duced the amplitude of HFS potentiation, which could develop fully at the d rug washout or decline to zero, becoming a short-term phenomenon, in the ca se of long-lasting PAF receptor block. Both drugs, when given after HFS, ha d no effect on the already established potentiation, but whilst BN-52021 sh owed an influence within 5 min of the LTP induction, carboxy-PTIO did not a ffect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP wh ich was associated with an increase in glutamate release as shown by reduct ion in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest th at NO and PAF are implicated as retrograde messengers in two different phas es of vestibular LTP: NO in the induction phase; and PAF in the full expres sion phase.