Fluoxetine enhances memory processing in mice

Flood, James F.; Cherkin, Arthur

doi:10.1007/bf02439584

Cited by 98 publications

(32 citation statements)

References 30 publications

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“…MAP4343 had persistent efficacy in recovering recognition memory deficits in isolated rats after either acute or subchronic treatment. In contrast, FLX was effective only after acute treatment, which is in agreement with studies reporting beneficial effects of a single injection of FLX on memory (18), whereas no effects were observed after repeated administrations (19). Moreover, MAP4343 rescued anxiety in isolated rats after subchronic treatment more efficaciously and more rapidly than FLX.…”

Section: Discussionsupporting

confidence: 88%

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

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Section: Discussionsupporting

confidence: 88%

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…As the drug was administered immediately after the training session, the present results cannot be attributed to unspecific effects, as may happen when drugs are administered before the training session (18). The effects of fluoxetine on inhibitory avoidance in this work are consistent with other reports (19,20,21) where systemic administration of the drug enhanced learning and memory in a dose-dependent fashion.…”

Section: Discussionsupporting

confidence: 94%

Acute effects of fluoxetine on inhibitory avoidance consolidation in male and female OF1 mice

Monleón

Casino

Vinader‐Caerols

et al. 2001

Neuroscience Res Communica

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SUMMARYThe effects of acute administration of fluoxetine on memory consolidation using an inhibitory avoidance task were investigated in male and female OF1 mice. Several doses of this antidepressant (5, 10, and 20 mg/kg) were intraperitoneally administered immediately after the training session. The test session was carried out four days later and response latencies were measured in both sessions. The results showed that the highest dose of fluoxetine significantly increased response latencies of inhibitory avoidance compared with the lowest dose and the control group. Sex differences in this task were observed, females showing a better performance. But the drug's effects were not sexually dimorphic: These sex differences were present in control animals, and they remained at every dose of fluoxetine. It is concluded that acute administration of fluoxetine did not impair inhibitory avoidance learning and it could be a better choice in depression and other disorders associated with memory deficits.

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“…Initial studies demonstrated that fluoxetine improved consolidation and retrieval memory in mice [86], yet subsequently, it was shown that acute administration of fluoxetine (5 and 10 mg/kg, 24 h prior to testing) improved the conditioned response to a unconditioned stimulus in a dose-dependent manner [87]. However, subsequent studies produced some uncertainty regarding the effect of fluoxetine on memory.…”

Section: Effect On Cognitionmentioning

confidence: 99%