An investigation of the mechanisms of delayed neurodegeneration caused by direct injection of quinolinate into the rat striatum in vivo

摘要: Abstract Injection of the N -methyl- d -aspartate receptor agonist quinolinate, or itself, into rat brain produces neurodegeneration which can be prevented by antagonists administered up to 5 h after excitotoxin injection. The present study was designed investigate aspects mechanisms involved in this delayed form neurodegeneration. Following its injection striatum, extracellular levels [ 3 H]quinolinate were monitored using a microdialysis probe located 1 mm from site Peak concentrations observed 10–20 min and decayed biexponential fashion, initial component having an apparent t 1/2 13.7 ± 5.2 ( n = 3). Estimations quinolinate 200 nmol indicated peak level 6.0 mM 3) at declined 1.2 0.13 2 substantial h, period over are effective model. Administration dizocilpine 1, 2, 100, 400 resulted similar temporal profile neuroprotection, as assessed measuring activities choline acetyltransferase glutamate decar☐ylase striatal homogenates, independent degree produced different doses. Overall, these results suggest that neuronal degeneration caused vivo is critically dependent upon events occurring excitoxin space. (10 mg/kg i.p.) intrastriatal trans -2,3-piperidine dicar☐ylate (100 nmol) reduced neurotoxicity, whereas smaller effect against neurotoxicity ibotenate nmol), perhaps indicating action sites other than receptor. competitive antagonist, 3-[(±)-2-car☐ypiperazin-4-yl]-propyl-1-phosphonate, quinolinate-induced dose-dependent manner with approximate Ed 50 value 30 (i.p., quinolinate). Haloperidol (O.5mg/kg i.p.), diazepam (10mg/kg, ifenprodil (50mg/kg quinolate failed reduce degeneration, suggesting blockade dopamine receptors, enhancement GABA-mediated inhibition occupation sigma does not prevent agonist.