Antidepressant-like effects in various mice strains in the forced swimming test.
BACKGROUND
Strain differences in mice have been reported in response to drugs in the mouse forced swimming test (FST), even if few antidepressants were examined.


OBJECTIVE
The aim of the present study was to investigate the influence of genetic factors, using five antidepressants (imipramine, desipramine, citalopram, paroxetine and bupropion) in the mouse FST, in outbred strains (Swiss, NMRI) and inbred strains (DBA/2, C57BL/6J Rj). Moreover, whole brain levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) in vehicle treated animals, which were or were not subjected to the FST, were measured by HPLC analysis in an attempt to explain behavioural differences.


METHODS
For each antidepressant, a dose range (1-16 mg/kg) was tested in the locomotor apparatus and only non-psychostimulant doses were then tested in the FST in order to detect antidepressant-like activity.


RESULTS
No baseline differences among Swiss, NMRI, DBA/2 and C57BL/6J Rj strains were observed in our experiments, allowing the comparison of different antidepressants in each strain. Imipramine (16 mg/kg), desipramine, citalopram (4-16 mg/kg) and paroxetine (8 and 16 mg/kg) treatment decreased the immobility time in the Swiss strain and the size of the effect reached more than 20% for each of these antidepressants. C57BL/6J Rj was the only strain sensitive to bupropion (2 and 4 mg/kg). In the NMRI strain, only paroxetine treatment decreased the immobility time (16 mg/kg).


CONCLUSIONS
Our study showed that drug sensitivity is genotype dependent. FST results have shown that Swiss mice are the most sensitive strain to detect 5-HT and/or NA treatment. The use of DBA/2 inbred mice may be limited, as an absence of antidepressant-like response was observed in the FST. The lack of sensitivity to antidepressant treatment in DBA/2 strains could be due to high DA, NA and 5-HT whole brain concentrations.
David
Denis Joseph Paul
DJ
EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, 1 rue Gaston Veil, BP 53508, 44035, Nantes Cedex 01, France.
Renard
Caroline E
CE
Jolliet
Pascale
P
Hascoët
Martine
M
Bourin
Michel
M
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018377:Neurotransmitter Agents / Q000378:metabolism; D013045:Species Specificity; D013550:Swimming
D000928:Antidepressive Agents; D018377:Neurotransmitter Agents