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Antidepressant efficacy screening of novel targets in the chick anxiety-depression model.
- Source :
-
Behavioural pharmacology [Behav Pharmacol] 2009 Mar; Vol. 20 (2), pp. 146-54. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Antidepressive Agents therapeutic use
Clinical Trials as Topic
Dose-Response Relationship, Drug
Male
Vocalization, Animal drug effects
Antidepressive Agents pharmacology
Anxiety drug therapy
Chickens
Depression drug therapy
Disease Models, Animal
Drug Evaluation, Preclinical methods
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5849
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Behavioural pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19300238
- Full Text :
- https://doi.org/10.1097/FBP.0b013e32832a8082