Prozac Research Today is a free monthly online journal that collates and summarizes the latest research about Prozac, including details on depression, side-effects, withdrawal, alternatives.

Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.

David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, Drew M, Craig DA, Guiard BP, Guilloux JP, Artymyshyn RP, Gardier AM, Gerald C, Antonijevic IA, Leonardo ED, Hen R

Université Paris-Sud EA 3544, Faculté de Pharmacie, Châtenay-Malabry Cedex F-92296, France. denis.david@u-psud.fr

Understanding the physiopathology of affective disorders and their treatment relies on the availability of experimental models that accurately mimic aspects of the disease. Here we describe a mouse model of an anxiety/depressive-like state induced by chronic corticosterone treatment. Furthermore, chronic antidepressant treatment reversed the behavioral dysfunctions and the inhibition of hippocampal neurogenesis induced by corticosterone treatment. In corticosterone-treated mice where hippocampal neurogenesis is abolished by X-irradiation, the efficacy of fluoxetine is blocked in some, but not all, behavioral paradigms, suggesting both neurogenesis-dependent and -independent mechanisms of antidepressant action. Finally, we identified a number of candidate genes, the expression of which is decreased by chronic corticosterone and normalized by chronic fluoxetine treatment selectively in the hypothalamus. Importantly, mice deficient in one of these genes, beta-arrestin 2, displayed a reduced response to fluoxetine in multiple tasks, suggesting that beta-arrestin signaling is necessary for the antidepressant effects of fluoxetine.

Published 29 May 2009 in Neuron, 62(4): 479-93.
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Articles on Prozac published 7 May 2009:

Gamma-aminobutyric acid amides of nortriptyline and fluoxetine display improved pain suppressing activity.   J Med Chem, 52(9): 3010-7.

The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively. Thus, 1 is a promising ... [Abstract] [Full-text]

Articles on Prozac published 2 April 2009:

Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study.   Am J Psychiatry, 166(4): 418-26.

OBJECTIVE: The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment. METHOD: Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report ... [Abstract] [Full-text]

Articles on Prozac published 16 March 2009:

Altered CB receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine.   J Neurochem, 108(6): 1423-33.

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After ... [Abstract] [Full-text]

Articles on Prozac published 3 March 2009:

Assessment of safety and long-term outcomes of initial treatment with placebo in TADS.   Am J Psychiatry, 166(3): 337-44.

OBJECTIVE: The authors examined whether initial assignment to receive placebo for 12 weeks followed by open active treatment as clinically indicated was associated with different levels of benefit and risk of harm across 36 weeks as compared with initial assignment to receive active treatments. METHOD: Adolescents with major depressive disorder (N=439) were randomly assigned to receive an initial 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy (CBT), combination treatment ... [Abstract] [Full-text]

Articles on Prozac published 16 February 2009:

Fluoxetine does not alter the ability of dopamine D(1)- and D(2)-like agonists to substitute for cocaine in squirrel monkeys.   Pharmacol Biochem Behav, 92(2): 219-23.

Fluoxetine has been shown to enhance several behavioral effects of cocaine, including its discriminative-stimulus effects. An interaction between increased serotonergic and dopaminergic actions produced by blockade of serotonin and dopamine reuptake, is one possible mechanism for the enhancement. The present study investigated the effects of fluoxetine on the cocaine-like discriminative-stimulus effects of the D(2)-like agonists quinpirole and (-)-NPA, and the D(1)-like agonist SKF 82958 in ... [Abstract] [Full-text]

Articles on Prozac published 2 February 2009:

Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze.   Brain Res Bull, 78(6): 323-7.

The elevated T-maze (ETM) is an animal model of anxiety-like behavior that assesses two different defensive behavioral tasks in the same animal-acquisition of inhibitory avoidance and latency to escape from an open and elevated arm. In rats, cute and chronic treatments with anxiolytic-like drugs impair avoidance acquisition while only chronic administration of panicolytic-like drugs impairs open arm withdrawal. To date, only the acute effects of anxiolytic/anxiogenic or panicolytic/panicogenic ... [Abstract] [Full-text]

Articles on Prozac published 29 January 2009:

Fluoxetine administration modulates the cytoskeletal microtubular system in the rat hippocampus.   Synapse, 63(4): 359-64.

A number of studies suggest that stressful conditions can induce structural alterations in the hippocampus and that antidepressant drugs may prevent such deficits. In particular, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was more effective in modulating different neuronal plasticity phenomena and related molecules in rat hippocampus. Cytoskeletal microtubule dynamics are fundamental to dendrites and axons remodeling, leading to the hypothesis that fluoxetine may affect the ... [Abstract] [Full-text]

Articles on Prozac published 28 January 2009:

On-line solid phase extraction coupled to capillary LC-ESI-MS for determination of fluoxetine in human blood plasma.   Talanta, 78(1): 295-9.

An instrumental setup including on-line solid phased extraction coupled to capillary liquid chromatography-electrospray ionization-mass spectrometry (SPE-capLC-ESI-MS) has been constructed to improve the sensitivity for quantification of fluoxetine hydrochloride in human plasma. Prior to injection, 0.5 mL of plasma spiked with metronidazole (internal standard) was mixed with ammonium formate buffer for effective chloroform liquid-liquid extraction. The method was validated in the range 5-60 ng ... [Abstract] [Full-text]

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