A chronic treatment with fluoxetine decreases 5-HT(1A) receptors labeling in mice selected as a genetic model of helplessness.
Two lines of mice were bred for their opposite helpless behavior in the tail suspension test, i.e., helpless (HL) mice and non helpless (NHL) mice. The 5-HT(1A) receptor labeling was quantified by means of autoradiography with (3)H-8-OH-DPAT on brain sections from mice of these two lines. We observed a significantly higher level of (3)H-8-OH-DPAT binding sites density in HL mice comparatively to NHL mice, in the medial prefrontal, cingulate, motor and sensorial cortices, in several regions of the limbic system, such as CA3 field of hippocampus, dentate gyrus, medial and baso-medial amygdala, and in dorsal and median raphe nuclei. A chronic 21-day treatment with the antidepressant fluoxetine (10 mg/kg, i.p. daily) attenuated significantly the spontaneous helplessness in HL mice but did not alter the behavior of NHL mice. In the brain of HL mice chronically injected with fluoxetine, the elevated (3)H-8-OH-DPAT binding sites density was no longer observed after treatment in several regions, among which the raphe nuclei. Conversely, the antidepressant treatment did not modify the (3)H-8-OH-DPAT binding sites density in NHL mice. The variation of 5-HT(1A) receptors binding density in the HL mice in response to a chronic fluoxetine treatment parallels the attenuation of the spontaneous helplessness observed in the tail suspension test, and may underlie this behavior.
Naudon
Laurent
L
Unité de Neuropsychopharmacologie Expérimentale, UMR 6036 CNRS-IFRMP No. 23, Faculté de Médecine et de Pharmacie de Rouen, 22 Boulevard Gambetta, 76183 Rouen, Cedex, France. laurent.naudon@ibaic.u-psud.fr
El Yacoubi
Malika
M
Vaugeois
Jean-Marie
JM
Leroux-Nicollet
Isabelle
I
Costentin
Jean
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006380:Helplessness, Learned; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005473:Fluoxetine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium