Differential increases in brain levels of neuropeptide Y and vasoactive intestinal polypeptide after kainic acid-induced seizures in the rat.
Changes in immunoreactivities of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were investigated in the brain of rats after severe kainic acid (KA, 10 mg/kg, i.p.) induced limbic seizures. Decreased levels of both neuropeptides were observed in the frontal cortex, straitum, dorsal hippocampus and amygdala/pyriform cortex subsequently to the period of acute seizures (3 h after injection of the toxin). Then NPY increased consistently in the frontal cortex, hippocampus and amygdala/pyriform cortex. Highest levels (290% of controls) were found in the frontal cortex after two months. Anticonvulsant therapy with phenobarbital (20 mg/kg, i.p., twice daily for three weeks) partially suppressed the rise in NPY levels. Immunoreactivity of VIP increased (to 150%) in the frontal cortex only transiently 3 days after injection of kainic acid. At the subsequently examined time intervals (10-60 days after kainic acid) it declined to control values. Levels decreasing subsequently to acute seizures reflect increased release and degradation of the respective peptide. Increased NPY levels suggest "upregulation" of NPY/somatostatin/GABA neurons due to the decreased seizure threshold of the animals. The early, reversible rise of VIP in the cortex points to a short-lasting activation of this peptide system contained in local cholinergic neurons. This may be a consequence either of the acute seizures or subsequent neuropathological changes.
Marksteiner
J
J
Department of Pharmacology, University of Innsbruck, Austria.
Sperk
G
G
Maas
D
D
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D007608:Kainic Acid; D008297:Male; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000378:metabolism*
D009478:Neuropeptide Y; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D007608:Kainic Acid; D010634:Phenobarbital