The prodynorphin system in the rat hippocampus is differentially influenced by kainic acid and pentetrazole.
Administration of kainic acid (15 mg/kg, i.p.) or pentetrazole (75 mg/kg, i.p.) to rats evoked recurrent limbic or tonic-clonic seizures, respectively. Radioimmunoassay showed that the level of alpha-neoendorphin (prodynorphin-derived peptide) in the hippocampus was decreased after 3 h (by c. 60%) and 72 h (by c. 40%), but was not changed after 24 h following kainic acid administration. The basal release of alpha-neoendorphin from hippocampal slices of kainic acid-treated rats was decreased after 3, 24 and 72 h following the drug injection by c. 50%. The K(+)-stimulated release was decreased after 3 and 24 h (by c. 300 and 200%, respectively) and was back to the control level after 72 h. An in situ hybridization study showed that kainic acid strongly enhanced the prodynorphin messenger RNA levels in the dentate gyrus after 3 and 24 h (by c. 200%), whereas after 72 h it tended to decrease. Twenty four hours after pentetrazole injection the hippocampal level of alpha-neoendorphin was elevated (by c. 33%) and remained unchanged after 3 and 72 h. No significant changes in the basal or K(+)-stimulated alpha-neoendorphin release from hippocampal slices of pentetrazole-treated rats were found at any time points measured. Three and 24 h after pentetrazole administration the level of prodynorphin mRNA in the dentate gyrus was slightly decreased (by c. 30%), but was back to the control values after 72 h. Hence seizure-related changes in hippocampal prodynorphin neuron activity seem to depend on the experimental model of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Lasoń
W
W
Department of Neuropeptides Research, Polish Academy of Sciences, Kraków.
Przewłocka
B
B
Przewłocki
R
R
D000818:Animals; D001345:Autoradiography; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013462:Sulfur Radioisotopes
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; C033660:preproenkephalin; D007608:Kainic Acid; D010433:Pentylenetetrazole