Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes.
ASC (Antidepressant-Sensitive Catalepsy) mice, bred for a high predisposition to catalepsy, are characterized by depression-like behavior and decreased immune responses. Chronic administration of fluoxetine, which is a selective serotonin reuptake inhibitor antidepressant widely used in clinical practice, to mice of this strain weakened catalepsy and normalized the number of rosette-forming cells in the spleen. In mice of the parental cataleptic strain CBA/Lac, fluoxetine had no effect on the level of catalepsy or the immune response. Analysis of the effects of fluoxetine on the functional activity of 5-HT(1A) and 5-HT(2A) receptors, and the expression of 5-HT(1A) receptor genes in the frontal cortex and midbrain and 5-HT(2A) receptors in the frontal cortex, as well as the tryptophan hydroxylase-2 and the serotonin transporter genes in the midbrain showed that the antidepressant had no effect on these parameters in ASC mice, but decreased the functional activity of 5-HT(2A) receptors in CBA/Lac mice. The possibility that the actions of fluoxetine on catalepsy and the immune response in mice with depression-like states are mediated via other serotoninergic mechanisms is discussed.
Tikhonova
M A
MA
Behavioral Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Siberia, Russia. mar-a-tikh@mail.ru
Alperina
E L
EL
Tolstikova
T G
TG
Bazovkina
D V
DV
Di
V Y
VY
Idova
G V
GV
Kulikov
A V
AV
Popova
N K
NK
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012397:Rosette Formation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000502:physiology*
D000928:Antidepressive Agents; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
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