The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D<sub>2</sub> dopamine receptors in the rat caudate putamen

Dziedzicka-Wasylewska, Marta; Rogoż, R.

doi:10.1038/sj.bjp.0701681

Cited by 9 publications

(4 citation statements)

References 48 publications

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“…In addition to the changes reported in the present studies, the NET À/À mice have been shown to be supersensitive to psychostimulants (Xu et al, 2000), a phenomenon that has been also observed following the repeated treatment with antidepressants (DziedzickaWasylewska and Rogoz ' , 1998;Maj et al, 1984;Rogoz ' and Dziedzicka-Wasylewska, 1999). More biochemical studies are necessary to elucidate further molecular mechanisms underlying these changes.…”

Section: Discussionsupporting

confidence: 66%

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Dziedzicka-Wasylewska

Faron-Górecka

Kuśmider

et al. 2006

Neuropsychopharmacol

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One of the main theories concerning the mechanism of action of antidepressant drugs (ADs) is based on the notion that the neurochemical background of depression involves an impairment of central noradrenergic transmission with a concomitant decrease of the norepinephrine (NE) in the synaptic gap. Many ADs increase synaptic NE availability by inhibition of the reuptake of NE. Using mice lacking NE transporter (NET À/À ) we examined their baseline phenotype as well as the response in the forced swim test (FST) and in the tail suspension test (TST) upon treatment with ADs that display different pharmacological profiles. In both tests, the NET À/À mice behaved like wild-type (WT) mice acutely treated with ADs. Autoradiographic studies showed decreased binding of the b-adrenergic ligand [ 3 H]CGP12177 in the cerebral cortex of NET À/À mice, indicating the changes at the level of b-adrenergic receptors similar to those obtained with ADs treatment. The binding of [ 3 H]prazosin to a 1 -adrenergic receptors in the cerebral cortex of NET À/À mice was also decreased, most probably as an adaptive response to the sustained elevation of extracellular NE levels observed in these mice. A pronounced NET knockout-induced shortening of the immobility time in the TST (by ca 50%) compared to WT mice was not reduced any further by NET-inhibiting ADs such as reboxetine, desipramine, and imipramine. Citalopram, which is devoid of affinity for the NET, exerted a significant reduction of immobility time in the NET À/À mice. In the FST, reboxetine, desipramine, imipramine, and citalopram administered acutely did not reduce any further the immobility time shortened by NET knockout itself (ca 25%); however, antidepressant-like action of repeatedly (7 days) administered desipramine was observed in NET À/À mice, indicating that the chronic presence of this drug may also affect other neurochemical targets involved in the behavioral reactions monitored by this test. From the present study, it may be concluded that mice lacking the NET may represent a good model of some aspects of depression-resistant behavior, paralleled with alterations in the expression of adrenergic receptors, which result as an adaptation to elevated levels of extracellular NE.

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Section: Discussionsupporting

confidence: 66%

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Dziedzicka-Wasylewska

Faron-Górecka

Kuśmider

et al. 2006

Neuropsychopharmacol

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“…Indeed, previous studies have reported that imipramine up-regulates DRD2 expression in the striatum (5,6), but no significant changes were observed in our study (Fig. 1).…”

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confidence: 50%

Pramipexole Upregulates Dopamine Receptor D2 and D3 Expression in Rat Striatum

et al. 2012

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Pramipexole is a dopamine agonist used for the treatment of Parkinson's disease. Among the members of the dopamine D 2 -like-receptor family (1), pramipexole showed higher selectivity for the dopamine receptor D 3 (DRD3) than for dopamine receptor D 2 (DRD2) and D 4 (2). Despite this affinity profile, it has been assumed that the antiparkinsonian activity of pramipexole is mainly due to DRD2 stimulation, while the role of DRD3 remains unclear (3). The aim of the current study was to investigate the effects of pramipexole on DRD2 and DRD3 expression profiles to reveal potential and additional functions for this dopamine agonist in the field of neuropharmacology.Male Wistar rats (8-week-old) were purchased from CLEA, Inc. (Tokyo). The animals were housed two per cage under controlled environmental conditions (temperature of 24°C ± 2°C, humidity of 50% ± 5%, and 7 AM -7 PM / 7 PM -7 AM light/dark cycle). The animals had free access to food and water. Pramipexole monohydrate was generously provided from Boehringer Ingelheim GmbH (Ingelheim, Germany). Imipramine hydrochloride (Wako Pure Chemical Industries, Ltd., Osaka) and bromocriptine mesylate (Sigma-Aldrich Corp., St. Louis, MO, USA) were purchased commercially. Pramipexole and imipramine were dissolved in 0.9% saline and injected subcutaneously. Bromocriptine was ultrasonically diffused in 0.25% methyl cellulose 400 solution (Wako Pure Chemical Industries, Ltd.).In Experiment 1, nine rats (298 -336 g) received pramipexole at 1 mg/kg or imipramine at 10 mg/kg in a volume of 1 ml/kg subcutaneously twice daily at 9 AM and 4 PM for 14 days. Nine control rats (288 -312 g) received 1 ml/kg 0.9% saline alone using the same schedule.In Experiment 2, ten rats (262 -284 g) received bromocriptine at 5 mg/kg in a volume of 1 ml intraperitoneally twice daily at 9 AM and 4 PM for 14 days. Ten control rats (266 -282 g) received 1 ml/kg 0.25% methyl cellulose 400 using the same schedule.The brains were dissected out on the day after the final injection, and the hypothalamus and striatum were isolated. Isolated brain tissues were immediately treated with the RNAlater TM RNA stabilization reagent (Qiagen GmbH, Hilden, Germany) and incubated overnight at 4°C. The solution was then removed and tissues were stored at −80°C until assayed. Medicine, Toon, Ehime 791-0295, Japan Received April 16, 2012; Accepted August 17, 2012 Abstract. Randomized clinical trials have shown that pramipexole has an antidepressant effect in patients with Parkinson's disease. We investigated the comparative efficacy of pramipexole toward dopamine receptor D 2 and D 3 expression in rat brain. Groups of rats were treated subacutely with pramipexole (1 mg/kg), imipramine (10 mg/kg), or bromocriptine (5 mg/kg), with appropriate controls. Using real-time RT-PCR and immunoblotting, dopamine receptor D 2 and D 3 expression was up-regulated in the striatum following pramipexole treatment, while imipramine and bromocriptine had no significant effects. These findings support that pramipexole exerts additional...

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“…On the other hand, hypoxia is reported to serve as a factor in the upregulation of β-AR [33], so that the hypoxic environment in HCC may lead to functional alterations in intracellular signal transduction systems which indeed are associated with receptor upregulation [34,35,36]. …”

Section: Discussionmentioning

confidence: 99%

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

Kassahun¹,

Guenl²,

Ungemach

et al. 2012

Pharmacology

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Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. There are now multiple lines of evidence demonstrating that the β-adrenoceptor (β-AR) signaling plays an important role in the progression and metastasis of cancer and may become a novel target for cancer therapy. Little information exists regarding the status of β-ARs and their postreceptor intracellular signaling cascade in the development of human HCC. This study was conducted to detect the expression signal transduction of the β-ARs in liver membranes obtained from patients with HCC and elucidate their possible implication on HCC development. Methods: The β-AR density and subtype distribution were determined by receptor binding studies. Protein levels of the β₂-AR and G_s_α protein were determined by Western blot analysis. The receptor coupling efficiency and biochemical activities of the adenylate cyclase (AC) was also determined. Results: In HCC liver membranes, the β₂-AR density was higher than the density in the nonadjacent nontumor liver membranes. The β₂-AR protein expression was 1.5-fold increased as compared with nonmalignant controls, and positively correlated with the receptor density. The G_s_α protein expression as well as the receptor, AC and G protein-stimulated activation of the cAMP formation was reduced in HCC. Conclusion: The β₂-AR was upregulated in human HCC. Despite this upregulation of the receptor, there was an altered postreceptor signal transduction in HCC liver. The mechanisms responsible for this change in the growth of HCC and the nature of this alteration remain unclear.

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The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D₂ dopamine receptors in the rat caudate putamen

Cited by 9 publications

References 48 publications

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Pramipexole Upregulates Dopamine Receptor D2 and D3 Expression in Rat Striatum

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

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The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D2 dopamine receptors in the rat caudate putamen

Cited by 9 publications

References 48 publications

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Effect of Antidepressant Drugs in Mice Lacking the Norepinephrine Transporter

Pramipexole Upregulates Dopamine Receptor D2 and D3 Expression in Rat Striatum

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

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The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D₂ dopamine receptors in the rat caudate putamen