fluvoxamine and nisoxetine

Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

Topics: Animals; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depression; Desipramine; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred ICR; Motor Activity; Norepinephrine Plasma Membrane Transport Proteins; Serotonin Plasma Membrane Transport Proteins; Species Specificity; Swimming

It has previously been found that a number of typical and atypical antidepressants, given chronically, intensify clonidine-induced aggressiveness in mice. Further experiments now show that chronic, but not acute, administration of nisoxetine, a selective inhibitor of noradrenaline uptake, potentiates clonidine-induced aggressiveness. Citalopram and fluvoxamine, two selective inhibitors of serotonin uptake, have no such action. Of the two isomers of flupenthixol, only the trans-form potentiates clonidine-induced aggressiveness of chronic experiments. The cis-form induces an inhibiting effect. Clonidine-induced aggressiveness is also intensified by chronic, but not by acute, administration of pizotifen, an antagonist fo serotonin and noradrenaline. The results seem to support the previous hypothesis that potentiation of clonidine-induced aggressiveness is mediated by an alpha 1-adrenergic mechanism.

Topics: Aggression; Animals; Antidepressive Agents; Citalopram; Clonidine; Drug Interactions; Fluoxetine; Flupenthixol; Fluvoxamine; Humans; Male; Mice; Oximes; Pizotyline; Propylamines; Stereoisomerism