Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test
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Variations in the effects of antidepressant drugs between different mouse strains are important for drug discovery and could lead to the identification of genes that predict differences in drug efficacy.
This study compared behavioral baselines and dose-dependent responses to the selective serotonin reuptake inhibitor (SSRI) citalopram in eight inbred mouse strains (C57BL/6J, DBA/2J, C3H/HeJ, BALB/cJ, A/J, 129/SvEmsJ, 129/SvImJ, and BTBR) using the tail suspension test (TST).
The DBA/2J, BALB/cJ, and BTBR strains were the most responsive to the effects of citalopram. Citalopram was least effective in the C57BL/6J and A/J strains. The antidepressant-like effects of citalopram in the TST were not correlated with changes in locomotor activity or deprivation-induced feeding behavior across the individual mouse strains, suggesting that patterns of sensitivity to citalopram are behaviorally specific and unlikely to result from pharmacokinetic variables. As an initial search for genetic polymorphisms causing differences in citalopram sensitivity, polymorphic forms of the tryptophan hydroxylase 2 (tph2) gene were genotyped and found to be not correlated with citalopram responsive (DBA/2J and BALB/cJ) and nonresponsive (A/J and C57BL/6J) strains.
The TST strain survey described here: (1) suggested the most appropriate strains for screening potential antidepressants, (2) identified parental strains appropriate for quantitative trait loci mapping of genomic loci regulating SSRI sensitivity, and (3) indicated appropriate background strains for measuring an antidepressant-like response to the SSRI citalopram. The pattern of response agrees with a previous mouse strain survey that examined sensitivity to fluoxetine in the forced swim test (Lucki I, Dalvi A, Mayorga AJ (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology 155:315–322).
KeywordsTail suspension test Depression Citalopram Genetics Pharmacogenetics Mouse
The authors would like to thank Dr. Wade Berrettini for guidance with this project. This research was supported by NIH grants MH14654 and MH48152.
- Arias B, Catalan R, Gasto C, Imaz ML, Gutierrez B, Pintor L et al (2001) Genetic variability in the promoter region of the serotonin transporter gene is associated with clinical remission of major depression after long-term treatment with citalopram. World J Biol Psychiatry 2:9SCrossRefGoogle Scholar
- Brocco M, Dekeyne A, Veiga S, Girardon S, Millan MJ (2002) Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents. Pharmacol Biochem Behav 71:667–680CrossRefPubMedGoogle Scholar
- Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev in pressGoogle Scholar
- Ripoll N, David DJ, Dailly E, Hascoet M, Bourin M (2003) Antidepressant-like effects in various mice strains in the tail suspension test. Behav Brain Res 3633:1–8Google Scholar