title: Administration of antisense DNA for hepatocyte growth factor causes an depressive and anxiogenic response in rats.
abstract: Hepatocyte growth factor (HGF) is induced in neurons during ischemia and is neuroprotective against post-ischemic delayed neuronal death in the hippocampus. HGF might play an important role in the maturation and functioning of these neurons in the hippocampus. Our aim was to determine what effect HGF antisense has on depression and anxiety in rats. HGF antisense was infused at a constant rate into cerebral lateral ventricles and its effect on anxiety in rats was monitored. In forced swimming test, rats that received antisense DNA increased the length of time that they were immobile in the water. In the elevated plus maze test, the black and white box test and conditioned fear test, HGF antisense administration caused all indicators of anxiety to increase. Number of HGF-positive cells in C1 of hippocampus was significantly decreased in the HGF antisense-infused group compared to the vehicle- and scrambled oligonucleotide-treated group. No significant effect on general locomotor activity was seen. These results indicate that inhibition of HGF induces an increase in depression and anxiety-related behaviors suggesting a depressive and anxiogenic-like effect.
authors.affiliation: Department of Neuropsychiatry, Oita Medical University, Hasama-Machi, Oita 879-5593, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Wakatsuki
authors.forename: Jotaro
authors.initials: J
authors.lastname: Akiyoshi
authors.forename: Shugo
authors.initials: S
authors.lastname: Ichioka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Jusen
authors.initials: J
authors.lastname: Tsuru
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsushita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hanada
authors.forename: Koichi
authors.initials: K
authors.lastname: Isogawa
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D016373:DNA, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000139:chemically induced*; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D020547:Lateral Ventricles; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016373:DNA, Antisense; D017228:Hepatocyte Growth Factor