Experimental anxiety and antidepressant drugs: the effects of moclobemide, a selective reversible MAO-A inhibitor, fluoxetine and imipramine in mice

Abstract

Available evidence derived from behavioural and clinical studies indicates that antidepressant drugs may be effective as anxiolytic agents. In this connection, the present study was designed to assess the behavioural effects of three antidepressant drugs, i.e. imipramine (IMI), a non selective serotonin (5-HT) and noradrenaline re-uptake (NA) inhibitor, fluoxetine (FLU), a selective 5-HT re-uptake inhibitor (SSRI) and moclobemide (MOC), a reversible inhibitor of type A monoamine-oxidase enzyme (RIMA) on anxiety, exploratory and locomotor activities in mice. The experiments used two animal models which attempt to separate these three factors: the "light-dark aversion" test and the "open-field" test. Naive female CD1 mice were administered intraperitoneally (i.p.) 30 min before testing with IMI (10, 20 and 40 mg/kg) or FLU (5, 10 and 20 mg/kg) or MOC (1, 5 and 10 mg/kg) or vehicle. Results showed that IMI (10 and 20 mg/kg), FLU (10 and 20 mg/kg) and MOC (1, 5 and 10 mg/kg) significantly reduced the aversive behavior of mice for the lit area in the light/dark aversion test, suggesting an anxiolytic-like effect. In fact, vehicle controls preferred the dark box where they spent approximately 70% of their time, indicating that light serves as an anxiogenic stimulus. Importantly, the anxiolytic-like effects of these antidepressant drugs were not associated with any increase in locomotor activity. In summary, these data suggest that FLU and the new generation of RIMA, exemplified by MOC, in terms of probable efficacy and greater safety, are of interest as treatment for a broad spectrum of anxiety disorders.

Anxiogenic-like effect of acute and chronic fluoxetine on rats tested on the elevated plus-maze

“…The same effects are observed in the noveltysuppressed feeding model of anxiety (23) and in the antipredator defensive behavior of mice (24). Vogels conflict test (22), however, yielded anxiolytic-like effects in rats, and so did another light aversion test (25). Effects of the same nature, albeit weak, were reported for the shock-induced ultrasonic vocalization test in rats (19,26).…”

Pharmacological modulation of anxiety-like phenotypes in adult zebrafish behavioral models

“…In rodents, MAOIs reduce anxiety-and depression-like behavior chronically (Crawley, 1985;Maki et al, 2000;Takamori et al, 2001) but yield conflicting results after acute administration, including both a lack of effects (Griebel et al, 1998(Griebel et al, , 1997Holmes and Rodgers, 2003;Lecci et al, 1990) and anxiolysis (de Angelis, 1996;Freund et al, 1979;Maki et al, 2000). Reducing anxiety in rodents (de Angelis, 1996;Freund et al, 1979;Maki et al, 2000;Negishi et al, 2004), a non-selective irreversible MAOI TCP produced similar anxiolytic-like responses in zebrafish ( Fig.…”

Antidepressant-like properties of three new α2-adrenoceptor antagonists

“…In this sense, further investigation of the possible dopaminergic effects induced by these new compounds might be necessary. Antidepressant agents may also be effective as anxiolytic agents in different anxiety animal models (De Angelis, 1996). For a further investigation of the pharmacological profile of these compounds, mice were submitted to the elevated plus maze test, which has been widely used for the evaluation of the anxiolytic-like properties of drugs (Lister, 1987).…”