Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test.
BACKGROUND
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.


OBJECTIVE
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).


RESULTS
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.


CONCLUSIONS
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).
Crowley
James J
JJ
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Blendy
Julie A
JA
Lucki
Irwin
I
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D011110:Polymorphism, Genetic; D013045:Species Specificity; D014365:Tryptophan Hydroxylase / Q000235:genetics
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase