Induction of pituitary adenylate cyclase-activating polypeptide mRNA in the medial parvocellular part of the paraventricular nucleus of rats following kainic-acid-induced seizure

We examined the effects of kainic acid (KA)-induced seizure on the expressi on of the pituitary adenylate cyclase-activating polypeptide (PACAP) gene i n the paraventricular nucleus (PVN) of rats using in situ hybridization his tochemistry. Subcutaneous administration of KA (12 mg/kg) in adult male Spr ague-Dawley rats caused a progressive development of seizure behavior. An i nduction of the PACAP gene expression in the medial parvocellular part of t he PVN (mpPVN) was observed 3, 6, 12, 24 and 48 h after subcutaneous admini stration of KA. From a nearly undetectable level, PACAP gene expression inc reased in the mpPVN and reached maximum 12 h after subcutaneous administrat ion of KA. PACAP gene expression returned to near basal level 48 h after st imulation with KA. Using a specific monoclonal PACAP antibody, PACAP immuno reactivity (-IR) gradually increased during the following 24 h after KA adm inistration. In controls, PACAP-IR was located exclusively in nerve fibers of the mpPVN, whereas KA administration induced PACAP-IR in cell bodies of the mpPVN, and a dense accumulation of PACAP-IR nerve fibers in the externa l zone of the median eminence was observed. Induction of the PACAP gene exp ression following KA-induced seizure was significantly reduced by pretreatm ent with diazepam or MK-801 (nonselective N-methly-D-aspartate receptor ant agonist). These results suggest that PACAP in the hypothalamo-adenohypophys ial system may have a hypophysiotropic role during KA-induced seizure. Copy right (C) 2000 S. Karger AG, Basel.