INFLUENCE OF ANXIOLYTIC DRUGS ON THE EFFECTS OF SPECIFIC SEROTONIN REUPTAKE INHIBITORS IN THE FORCED SWIMMING TEST IN MICE

This study aimed at investigating the effect of several selective sero tonin reuptake inhibitors (SSRIs), given alone or in combination with anxiolytic drugs, on the time spent immobile in the forced swimming te st in mice. The time spent immobile was dose-dependently reduced by ac ute administration of fluoxetine (4-64 mg/ kg, i.p.), paroxetine (1-32 mg/kg, s.c.) or sertraline (4-32 mg/kg, s.c.), indalpine was active a t only one dose (16 mg/kg, i.p.), fluvoxamine (up to 16 mg/kg, i.p.) a nd citalopram (up to 4 mg/kg, i.p.) were inactive. The anti-immobility effect of fluoxetine (32 mg/kg) was antagonized by an acute co-admini stration of all anxiolytics tested, the GABA(A)/BZD receptor agonists, diazepam (2 mg/kg, i.p.), chlordiazepoxide (8 mg/kg, i.p.), lorazepam (0.125 mg/kg, i.p.), triazolam (0.06 mg/kg, i.p.) and alpidem (8 mg/k g, i.p.) and the 5-HT1A receptor partial agonist, buspirone (0.5 mg/kg , s.c.). The sedative neuroleptic, thioridazine (4 mg/kg, i.p.), was a lso found to counteract the effect of fluoxetine. Lorazepam, triazolam and buspirone also reversed the anti-immobility effect of paroxetine and sertraline, while diazepam and chlordiazepoxide did not. Alpidem r educed the effect of sertraline but not paroxetine, whereas the revers e was found with thioridazine. These data indicate that the influence of anxiolytics on the action of SSRI antidepressants is variable, depe nding on both the SSRI and the anxiolytic considered. The co-administr ation of the GABA(A)/BZD receptor antagonist, flumazenil (16 mg/kg, i. p.), with behaviourally inactive doses of fluoxetine, fluvoxamine and citalopram, resulted in a reduction of immobility. The 5-HT1A receptor antagonist, (+)-WAY 100135 (8 mg/kg, s.c.), combined with a subactive dose of fluoxetine, but not with fluvoxamine, significantly reduced t he time spent immobile. The 5-HT2A receptor antagonist, ketanserin (32 mg/kg, s.c.), which reduced immobility when given alone, did not inte rfere with fluoxetine given at a subactive dose. Although non-specific sedative and/or motor effects cannot be totally ruled out, these resu lts suggest that pharmacodynamic interactions exist between various an xiolytics and SSRIs. These interactions probably involve both serotone rgic and GABAergic processes.