Involvement of the 5-HT(1A) receptor in the anti-immobility effects of fluvoxamine in the forced swimming test and mouse strain differences in 5-HT(1A) receptor binding.
We previously demonstrated the presence of strain differences in baseline immobility time and sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in five strains of mice (ICR, ddY, C57BL, DBA/2 and BALB/c mice). Furthermore, variations in serotonin (5-HT) transporter binding in the brain were strongly related to strain differences in baseline immobility and sensitivity to fluvoxamine. In the present study, we examined the involvement of the 5-HT(1A) receptor in anti-immobility effects in DBA/2 mice, which show high sensitivity to fluvoxamine. The anti-immobility effects of fluvoxamine in DBA/2 mice were inhibited by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT(1B) receptor antagonist 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide (GR55562), the 5-HT(2) receptor antagonist 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT(3) receptor antagonist ondansetron and the 5-HT(4) receptor antagonist 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not influence the anti-immobility effects of fluvoxamine in DBA/2 mice. These results suggest that fluvoxamine-induced antidepressant-like effects in DBA/2 mice are mediated by the 5-HT(1A) receptor. We analyzed 5-HT(1A) receptor binding in the brains of five strains of mice. Strain differences in 5-HT(1A) receptor binding were observed. 5-HT(1A) receptor binding in brain was not correlated with baseline immobility time in the five strains of mice examined. These results suggest that, although the anti-immobility effects of fluvoxamine in DBA/2 mice are mediated by the 5-HT(1A) receptor, strain differences in 5-HT(1A) receptor binding are not related to variation in immobility time and responses to fluvoxamine.
Sugimoto
Yumi
Y
Laboratory of Pharmacology, Department of Clinical Pharmacy, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan. yumisugi@hamayaku.ac.jp
Furutani
Sachiko
S
Kajiwara
Yoshinobu
Y
Hirano
Kazufumi
K
Yamada
Shizuo
S
Tagawa
Noriko
N
Kobayashi
Yoshiharu
Y
Hotta
Yoshihiro
Y
Yamada
Jun
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013045:Species Specificity; D013550:Swimming; D013997:Time Factors
D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D016666:Fluvoxamine