title: Lack of effect of secretin on kindling and seizures.
abstract: Secretin infused into rats activates neurons located in brain areas controlling autonomic function and emotion. The brain activity of secretin is mediated, at least in part, through vagal pathways. It is known that afferent stimulation of the vagus nerve results in considerable antiepileptic effects. Whether or not secretin has an effect on seizures is unknown. In this study, we evaluated the efficacy and safety of secretin as an antiepileptogenic agent in electrical kindling and as an anticonvulsant in fully kindled seizures. To assess antiepileptogenic effects, we administered secretin (10, 30, or 100 microg/kg/dose) or normal saline intravenously 5 min before twice-daily kindling stimulation. To assess the anticonvulsant effect of secretin, we administered either normal saline or secretin (100 microg/kg/dose) 5 min before the electrical stimulation to fully kindled rats. We observed no effect on kindling rate or afterdischarge duration. In fully kindled rats, secretin administration had no effect on kindling stage or afterdischarge duration. Thus, in the dose range used in this preliminary acute treatment study, secretin had no discernible antiepileptogenic or anticonvulsant effects. Secretin was very well tolerated in this multidose protocol.
authors.affiliation: Neuroscience Center at Dartmouth, Section of Neurology, Dartmouth Medical School, Lebanon, NH, USA. qian.zhao@Dartmouth.edu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Richard
authors.initials: R
authors.lastname: Boismenu
authors.forename: James R
authors.initials: JR
authors.lastname: Rusche
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000927:Anticonvulsants; D012633:Secretin