title: 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.
abstract: 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.
authors.affiliation: Behavioral Neurogenomics Laboratory, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Siberia, Russia. mar-a-tikh@mail.ru
authors.forename: M A
authors.initials: MA
authors.lastname: Tikhonova
authors.forename: E L
authors.initials: EL
authors.lastname: Alperina
authors.forename: T G
authors.initials: TG
authors.lastname: Tolstikova
authors.forename: D V
authors.initials: DV
authors.lastname: Bazovkina
authors.forename: V Y
authors.initials: VY
authors.lastname: Di
authors.forename: G V
authors.initials: GV
authors.lastname: Idova
authors.forename: A V
authors.initials: AV
authors.lastname: Kulikov
authors.forename: N K
authors.initials: NK
authors.lastname: Popova
mesh_terms: 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*
chemical_list: 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
references.citation: Neuron. 2005 Jan 6;45(1):11-6
references.pmid: 15629698
references.citation: Genetika. 2005 Sep;41(9):1222-8
references.pmid: 16240633
references.citation: J Neurosci. 1999 Dec 1;19(23):10494-501
references.pmid: 10575045
references.citation: Mol Interv. 2004 Apr;4(2):109-23
references.pmid: 15087484
references.citation: Clin Neurosci Res. 2006 Aug;6(1-2):52-68
references.pmid: 18079991
references.citation: Genes Brain Behav. 2008 Jun;7(4):506-12
references.pmid: 18194468
references.citation: Int J Neurosci. 2004 Sep;114(9):1049-62
references.pmid: 15370173
references.citation: J Neurosci Methods. 2005 Jan 30;141(1):97-101
references.pmid: 15585293
references.citation: Mol Psychiatry. 2005 Aug;10(8):782-9, 714
references.pmid: 15940298
references.citation: J Neurochem. 1993 Oct;61(4):1270-6
references.pmid: 8376984
references.citation: Science. 2004 Jul 9;305(5681):217
references.pmid: 15247473
references.citation: J Neurosci Methods. 2008 May 30;170(2):345-51
references.pmid: 18342949
references.citation: Br J Pharmacol. 1992 Sep;107(1):15-21
references.pmid: 1422568
references.citation: Genetika. 2004 Jun;40(6):779-86
references.pmid: 15341268
references.citation: Eur Neuropsychopharmacol. 1993 Jun;3(2):85-94
references.pmid: 8364353
references.citation: Pharmacol Ther. 1990;45(3):425-55
references.pmid: 2405444
references.citation: Neurosci Behav Physiol. 2006 Sep;36(7):703-7
references.pmid: 16841149
references.citation: Psychosom Med. 2002 Mar-Apr;64(2):267-73
references.pmid: 11914442
references.citation: Brain Res. 1994 Jan 7;633(1-2):267-74
references.pmid: 8137161
references.citation: Trends Pharmacol Sci. 1994 Jul;15(7):220-6
references.pmid: 7940983
references.citation: Science. 2003 Jan 3;299(5603):76
references.pmid: 12511643