Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: an in vivo study in the dentate gyrus of the rat.
The dentate gyrus of anaesthetized rats was perfused with artificial cerebrospinal fluid while field responses evoked by stimulation of the perforant path were monitored. Perfusates were collected for analysis of endogenous glutamate, aspartate and arachidonate. In animals in which long-term potentiation was induced by tetanic stimulation, there was a sustained increase in the concentration of glutamate in the perfusate, and, less reliably, in aspartate, as previously reported by Bliss et al. (J. Physiol., Lond. 377, 391-408, 1986) and Errington et al. (Neuroscience 20, 279-284, 1987). The lipoxygenase and phospholipase A2 inhibitor nordihydroguaiaretic acid, when added to the perfusate 30 min before the tetanus, abolished both long-term potentiation of the population excitatory postsynaptic potential and the tetanus-induced increase in glutamate release. Long-term potentiation of the population spike was reduced but not abolished. There was also a sustained increase in the release of arachidonic acid following the induction of long-term potentiation which did not occur when induction was blocked by nordihydroguaiaretic acid. These results are discussed in the light of the possibility that arachidonic acid or one of its lipoxygenase metabolites may be the retrograde messenger which we have postulated is released from postsynaptic sites following tetanic stimulation to trigger increased transmitter release from presynaptic terminals.
Lynch
M A
MA
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, London, U.K.
Errington
M L
ML
Bliss
T V
TV
D000200:Action Potentials / Q000187:drug effects; D000222:Adaptation, Physiological; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology*; D004558:Electric Stimulation; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D002396:Catechols; D005971:Glutamates; D016718:Arachidonic Acid; D018698:Glutamic Acid; D009637:Masoprocol