NMDA-induced preconditioning attenuates synaptic plasticity in the rat hippocampus.
It was recently demonstrated that glutamate could precondition hippocampal slices against the damaging effects of hypoxia, and we have now extended this observation by investigating (i) the ability of glutamate receptor agonists to act as preconditioning agents and (ii) the effects of preconditioning on synaptic plasticity. Using rat hippocampal slices, 15 microM NMDA applied for 10 min (chemical insult) caused abolition of the population spike potentials (PS) followed by approximately 33% recovery at 60 min post-insult. In comparison, a 5 min preconditioning exposure of 10 microM NMDA given 30 min prior to the insult significantly improved the recovery to 69%. Preconditioning did not alter paired pulse facilitation; however, it significantly enhanced paired pulse depression and reduced population spike long-term potentiation (PS-LTP) and LTP in field recordings. This effect on PS-LTP appeared to be NMDA receptor dependent and was blocked by the nitric oxide synthase inhibitors nitro-L-arginine methyl ester (L-NAME) and 7-nitro indazole (7-NI) but not by the adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We conclude that preconditioning by NMDA can improve recovery following acute insults but may have deleterious effects on neuronal plasticity.
Department of Preclinical Sciences, Faculty of Medical Sciences, University of the West Indies, St. Augustine Campus, Trinidad and Tobago. fmyoussef@tstt.net.tt
Farid F
FF
Youssef
Jonas I
JI
Addae
Trevor W
TW
Stone
D000200:Action Potentials / Q000187:drug effects; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D014970:Xanthines; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D014633:Valine; D019331:NG-Nitroarginine Methyl Ester