Antidepressant efficacy screening of novel targets in the chick anxiety-depression model

Abstract

The chick anxiety-depression model is a hybrid simulation, which may prove useful as an early preclinical dual pharmacological screen for novel therapeutics. Separate dose-response studies were conducted with seven test compounds that have screened positive for antidepressant effects in rodent depression models and included prasterone (5.0-40.0 mg/kg), memantine (2.5-20.0 mg/kg), ketamine (1.0-10.0 mg/kg), mifepristone (50.0-400.0 mg/kg), DOV216,303 (5.0-20.0 mg/kg), CGP36742 (2.5-15.0 mg/kg), and antalarmin (1.0-30.0 mg/kg). Chicks aged 4-6 days posthatch received test compounds intramuscularly 15 min before social separation, in which distress vocalization rates were recorded. High rates of vocalization in the first phase (0-5 min) of social separation seem to model an anxiety-like state and lower rates of vocalization in the second phase (30-60 min) seem to model a depression-like state. Prasterone, memantine, ketamine, and DOV216,303 attenuated and CPG36742 enhanced the pattern of vocalizations in the first phase. Prasterone, ketamine, mifepristone, DOV216,303, and CPG36742 attenuated and memantine and antalarmin enhanced the pattern of vocalizations in the second phase. This pattern of drug effects parallels what clinical data exist, and highlights two important characteristics of this dual-screening assay. For the compounds tested, this chick model identified phase II and III clinical failures (e.g. memantine and antalarmin) and has the potential to reveal possible contraindications of compounds (i.e. CPG36742) in cases where anxiety symptoms are concomitant with a depressive episode.

An attention bias test to assess anxiety states in laying hens

“…A 20-min waiting interval for the drug to take effect was determined based on rat studies with m -CPP (Bilkei-Gorzó, Gyertyán & Lévay, 1998). Previous drug studies with young chicks have applied a 15-min waiting interval (Sufka et al, 2009; Hymel & Sufka, 2012) but there has been no previous application of m -CPP on adult hens. The same waiting interval was applied to birds injected with saline.…”

Pharmacological modulation of anxiety-like phenotypes in adult zebrafish behavioral models

“…For example, N-methyl D-aspartate (NMDA) receptor antagonist ketamine produces robust behavioral activation in adult zebrafish (Zakhary et al, 2011), strikingly paralleling the drug's hyperlocomotory effects in rodents (da Irifune et al, 1998). Although ketamine has anxiolytic-like action on clinical (Irwin and Iglewicz, 2010) and animal (Engin et al, 2009;Pietersen et al, 2006;Sufka et al, 2009) anxiety, anxiogenic effects were also reported in rodents (da . Therefore, this aspect of ketamine's behavioral pharmacology remains to be explored in zebrafish in detail.…”

Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability

“…However, there is considerable interest in using mifepristone to treat some forms of depression (see Benagiano et al, 2008b; Flores et al, 2006), stemming from the fact that it is also a glucocorticoid receptor antagonist (Attardi et al, 2004; Benagiano et al, 2008a). Recent studies have shown antidepressant-like effects of mifepristone in mice (Galeeva et al, 2007), rats (Korte et al, 1996; Wulsin et al, 2010), and chicks (Sufka et al, 2009). …”