The behavioral profiles of five clinically used selective serotonin reuptake inhibitors (SSRIs) citalopram, paroxetine, sertraline,
fluvoxamine and fluoxetine, have been compared in animal models of antidepressant (mouse forced swim test), anxiolytic (exploration
of black and white test box and foot-shock-induced ultrasonic vocalization in the rat) and antiaggressive (isolation-induced
aggressive behavior in the mouse) activity. The results are discussed in relation to receptor binding data from the literature.
Furthermore, affinities for the
σ
1 and
σ
2 binding sites are presented. Citalopram reversed the immobility induced by forced swimming with a potency similar to that
of imipramine. Paroxetine, fluvoxamine and fluoxetine reversed swim-induced immobility less potently and with a maximum of
40–50% reversal. Citalopram produced a mixed anxiogenic-/anxiolyticlike response in rats tested in the two-compartment black
and white box. Paroxetine induced an anxiogenic-like response at low doses and the other SSRIs were without major effects.
Citalopram and paroxetine inhibited footshock-induced ultrasonic vocalization with high potencies. The dose-response curve
was biphasic for citalopram with a maximum of 64% inhibition. Sertraline and fluvoxamine inhibited the vocalization less potently,
and fluoxetine induced a weak inhibitory effect corresponding to a maximum of 32%. Sertraline, fluvoxamine and fluoxetine
inhibited isolation-induced aggressive behavior, whereas citalopram and paroxetine were inactive. Both 5-HT
1 and 5-HT
2 receptors are involved, and there was a functional interaction between 5-HT
1A and 5-HT
2A or 5-HT
2C receptors, as ritanserin potentiated the antiaggressive effect of 1,5-HTP as well as that of 8-OH-DPAT.
Key words Serotonin reuptake inhibitors - Depression - Anxiety - Aggression - Rodents