Differential behavioral syndrome evoked in the rats after multiple doses of SSRI fluoxetine with selective MAO inhibitors rasagiline or selegiline

Abstract

This study investigated whether rasagiline and selegiline (MAO-B inhibitors) induce serotonin syndrome in fluoxetine-treated rats. Rats received rasagiline (0.1, 0.5, 2.0 mg/kg), or selegiline (0.8, 4.0, 16.0 mg/kg) (doses reflecting the clinical ratio of 1:8 base) in drinking water for 28 days. During the last 21 days, they received injections of fluoxetine 10 mg/kg (controls received water only, then saline injections; a fluoxetine only group received water only then fluoxetine). Serotonin syndrome was assessed using neurological severity score (NSS), food intake and weight gain. Mean NSS significantly increased, and weight and food consumption significantly decreased in rats receiving fluoxetine alone compared with controls. Selegiline 16 mg/kg but not rasagiline (regardless of dose) exacerbated these effects. We concluded that selegiline's amphetamine-like metabolites may increase synaptic cathecholamines and possibly serotonin, aggravating fluoxetine's effect. Rasagiline is devoid of this effect and may therefore be safer for use with serotonergic drugs in parkinsonian patients.

Effects of prolonged selective serotonin reuptake inhibition on the development and expression of l-DOPA-induced dyskinesia in hemi-parkinsonian rats

“…By comparison, L-DOPA efficacy was observed on the first day of testing in L-DOPA-naïve rats regardless of SSRI dose and this was maintained over 3 weeks. Though adverse side effects have been reported in PD patients and rodent models treated with SSRIs no such observations were made in the present study (Linazasoro 2000; Speiser et al, 2008). From a translational point of view, that recurrently administered SSRIs not only reduced LID, but also maintained L-DOPA’s anti-parkinsonian efficacy is an attractive feature of this strategy.…”

Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study

“…Bairy et al concluded that prenatal fluoxetine administered to rats caused weight loss and a delay in the transient motor development of fetuses, although it did not, however, compromise postnatal behavior, thus supporting the findings of Speiser et al 21,29 Most studies demonstrate that fluoxetine-treated rats bear low weight offspring. Vartazarmian et al, however, found no weight alterations in fetuses of fluoxetine-treated rats.…”

Serotonin Toxicity Association with Concomitant Antidepressants and Rasagiline Treatment: Retrospective Study (STACCATO)

“…Experimental studies in animal models and healthy human subjects have reported that the coadministration of rasagiline and serotonergic antidepressants does not induce STS . Several investigators have characterized and summarized the tolerability profile of concurrent rasagiline and antidepressants (R+ADT) in patients with PD .…”