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Repeated treatment with mirtazapine induces brain-derived neurotrophic factor gene expression in rats

100%

Rogoz Z., Skuza G., Legutko B.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 4

Recent studies indicate a role of the brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, as well as in the mechanism of action of antidepressant drugs (ADs). It has been shown that serum BDNF levels are decreased in depressed patients. Moreover, antidepressant treatment increases serum BDNF levels and it is positively correlated with medication response. In addition, repeated administration of ADs induces an increase in rat hippocampal or cortical BDNF gene expression. Since the most potent effect of ADs on BDNF gene expression was found after prolonged treatment, in the present study we investigated the influence of repeated treatment (twice daily for 14 days) of the new AD mirtazapine (5 or 10 mg/kg) on BDNF mRNA level (the Northern blot) in rat hippocampus and cerebral cortex. Imipramine was used as a reference compound. The experiment was carried out on male Wistar rats. The tissue for biochemical assays was collected 24 h after the last doses of mirtazapine and imipramine. We also studied the effect of repeated mirtazapine on the action of the 5-HT2A receptor agonist (±)DOI in the behavioral test (head twitches induced by (±)DOI) in rats. The obtained results showed that, like imipramine (10 mg/kg), mirtazapine (10 mg/kg) increased BDNF gene expression in both the examined brain regions: in the hippocampus by 24.0 and 26.5%, in the cerebral cortex by 29.9 and 41.5%, respectively, compared with the vehicle-treated control. Neither mirtazapine nor imipramine administered repeatedly at a lower dose (5 mg/kg) significantly changed BDNF mRNA levels in the hippocampus and cerebral cortex. Repeated treatment with mirtazapine (10, but not 5 mg/kg) inhibited the behavioral syndrome induced by (±)DOI. This study provides first conclusive evidence that repeated mirtazapine administration increases BDNF mRNA levels; moreover, it indicates that the enhancement of BDNF gene expression may be essential for the clinical effect of mirtazapine.

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Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors

84%

Rogoz Z., Wrobel A., Dlaboga D., Maj J., Dziedzicka-Wasylewska M.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 1

Mirtazapine (MIR)is an antidepressant which enhances noradrenergic and serotonergic 5-HT1A neurotransmission via antagomism of central alpha2 - adrenergic autoreceptors and heteroreceptors.The drugs does not inhibit noradrenaline and serotonin reuptake but blocks the 5-HT2 and 5-HT3 receptors and has high affinity only for central and peripheral histamine H1 receptors.The present study was aimed at determining whether repeated MIR treatment induced adaptive changes in the alpha1 - adrenergic receptors,similar to those reported by us early for tricyclic antidepressants,The experiments were carried out on male mice and rats.MIR was administered at a dose of 10 mg/kg once or repeatedly (twice daily for 14 days).The obtained results showed that MIR administrated repeatedly potentiated the methoxamine-induced exploratory hyperactivity in rats and clonidine- induced aggressiveness in mice,those effects being mediated by alpha1 - adrenergic receptors. MIR given repeatedly (but not acutely)increased the binding (Bmax )of [3H ]prazosin to alpha1 - adrenergic receptors in cerebral cortex,however,the ability of the alpha1 - adrenoceptor agonist phenylephrine to compete for the these sites was not significantly changed.The above results indicate that repeated MIR administration increases the responsiveness of alpha1 - adrenergic system (behavioural and biochemical changes),as tricyclics do.However, the question whether the increased functional responsiveness found in the present study is important for the clinical antidepressant efficacy,remains open.

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Jak poradzić sobie z zaburzeniami łaknienia?

43%

Cook A. K.

Weterynaria po Dyplomie

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2019

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tom 20

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nr 5

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

1 Weterynaria po Dyplomie

2 Rogoz Z.

1 Cook A. K.

1 Dlaboga D.

1 Dziedzicka-Wasylewska M.

1 Legutko B.

1 Maj J.

1 Skuza G.

1 Wrobel A.

1 2019

1 2005

1 2002

Repeated treatment with mirtazapine induces brain-derived neurotrophic factor gene expression in rats

Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors

Jak poradzić sobie z zaburzeniami łaknienia?