Effects of Serotonergic Anxiolytics on the Freezing Behavior in the Elevated Open-Platform Test in Mice

Abstract

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-HT 1A -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 fearrelated behavior. In addition, this test is convenient for assaying anxiolytic drugs that affect serotonergic neurotransmission.

Chlorpheniramine exerts anxiolytic-like effects and activates prefrontal 5-HT systems in mice

“…These results suggest that, in addition to the 5-HT systems, the DA and NA systems might participate in the anxiolytic-like effects of chlorpheniramine. Recently, we indicate that a treatment with 5-HT synthesis inhibitor, pCPA, increased the duration of freezing in mice subjected to the elevated open-platform test (Miyata et al 2007a). In that report, we also indicated that the selective NA uptake inhibitor, reboxetine, and the non-selective 5-HT/NA uptake inhibitors tricyclic antidepressants, imipramine and clomipramine, did not affect the duration of freezing.…”

“…To evaluate the anxiolytic-like effects of chlorpheniramine, we used two different behavioral tests. The conditioned fear test detects the punishment-evoked anxiety of animals, which is sensitive, particularly to serotonergic anxiolytics (Tye et al 1977), and the elevated open-platform test that could predict anxiolytic-like effects (Miyata et al 2007a). The fact that chlorpheniramine reduced freezing in both tests might indicate that this antihistamine drug exerts anxiolytic-like effects.…”

“…The procedure was performed according to our previous report (Miyata et al 2007a). The experiment was conducted in a room illuminated by white fluorescent light (300 lux).…”

“…We recently established the elevated open-platform test to simply assess the behavioral response of mice to unconditioned psychological stress (Miyata et al 2007a, b). The SSRIs fluoxetine and citalopram significantly decreased the duration of freezing behavior in the elevated openplatform test (Miyata et al 2007a). In addition, 5-HT depletion by treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA) markedly increased the duration of freezing in the elevated open-platform test (Miyata et al 2007a).…”

“…The SSRIs fluoxetine and citalopram significantly decreased the duration of freezing behavior in the elevated openplatform test (Miyata et al 2007a). In addition, 5-HT depletion by treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA) markedly increased the duration of freezing in the elevated open-platform test (Miyata et al 2007a). Furthermore, streptozotocin-induced diabetic mice showed lengthened freezing behavior in the elevated open-platform test (Miyata et al 2007b).…”