title: Effects of serotonergic anxiolytics on the freezing behavior in the elevated open-platform test in mice.
abstract: Freezing behavior is thought to be a sign of fear in animals. We examined whether the freezing behavior during the elevated open-platform stress, which is a psychological stressor without painful stimulus, is modulated by serotonergic neurotransmission and would be a useful marker for screening anxiolytic and/or antidepressant. Male ICR mice (6 - 8-week-old) were individually placed on an elevated open-platform and the duration of freezing behavior of mouse was measured for 10 min. Fluoxetine and citalopram, selective serotonin (5-HT) reuptake inhibitors, markedly decreased the duration of freezing. Fenfluramine, a 5-HT releaser, and 8-OH-DPAT, a potent 5-HT1A-receptor agonist, also significantly decreased the duration of freezing. In contrast, the 5-HT-synthesis inhibitor p-chlorophenylalanine significantly increased the duration of freezing. Diazepam, a benzodiazepine anxiolytic, had no effect on the duration of freezing at doses having no effect on locomotor activity. Imipramine and clomipramine, tricyclic antidepressants, also did not affect the duration of freezing. Reboxetine, a selective noradrenaline reuptake inhibitor, significantly increased the duration of freezing. These results indicate that the activation of serotonergic neurotransmission attenuates the fear-related behavior in the elevated open-platform test, while the activation of noradrenergic neurotransmission increases the fear-related behavior. In addition, this test is convenient for assaying anxiolytic drugs that affect serotonergic neurotransmission.
authors.affiliation: Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo 142-8501, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Miyata
authors.forename: Toshiko
authors.initials: T
authors.lastname: Shimoi
authors.forename: Shoko
authors.initials: S
authors.lastname: Hirano
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamada
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hata
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Junzo
authors.initials: J
authors.lastname: Kamei
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015283:Citalopram; D005473:Fluoxetine; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors