Effects of Repeated Treatment With Fluoxetine and Citalopram, a 5-Ht Uptake Inhibitors on 5-Ht1a and 5-Ht2 Receptors in the Rat Brain.

Klimek, Violetta; Zak-Knapik, J.; Pietrasiewicz, Marzena

doi:10.1097/00002826-199202001-01149

Cited by 34 publications

(46 citation statements)

References 17 publications

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“…Welner et al (1989) observed a reduction in the dorsal raphe and decreased binding in midbrain was observed by Li et al (1994) after chronic fluoxetine. Changes have been reported by some authors in the hippocampus but are inconsistent, showing increased density (Klimek et al 1994) or decreased density and increased affinity (Maj et al 1996). However, Hensler et al (1991) failed to find binding changes in any brain area after chronic administration of the SSRIs, citalopram and sertraline, and a similar result was obtained by Li et al (1997) with paroxetine.…”

Section: Serotonergic Receptors Of the 5-ht 1a Subtype Have Been Suggmentioning

confidence: 68%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Neuropsychopharmacology

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Serotonergic receptors of the 5-HT 1A subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HTThere is considerable interest in the role of serotonergic (5-HT) receptors of the 5-HT 1A subtype in the therapeutic action of antidepressant drugs. 5-HT 1A receptors are located presynaptically on serotonergic cell bodies in the raphe nuclei where they serve as autoreceptors which inhibit cell firing and reduce 5-HT release by a negative feedback mechanism, and post-synaptically in the hippocampus, cortex and other brain areas, including the hypothalamus. Based on electrophysiological studies in rats, De Montigny and colleagues Mongeau et al. 1997) proposed that each major class of antidepressants increases 5-HT neurotransmission by a distinct mechanism involving either From the Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center (BL, YG, MEN) and the Laboratory of Applied Statistics, Hebrew University (MG), Jerusalem, Israel; the Endocrine Laboratory, Department of Medicine (BA) and Department of Psychiatry (KPL), University of Wuerzburg, Wuerzburg, Germany.Address correspondence to: Prof. Bernard Lerer, Biological Psychiatry Laboratory, Dept. of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.Received May 15, 1998; accepted August 25, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 Ipsapirone Challenge in Normal Subjects on Fluoxetine 629pre-or post-synaptic 5-HT 1A receptors. The selective serotonin re-uptake inhibitors (SSRIs), which raise 5-HT synaptic levels when given acutely, were proposed to increase 5-HT transmission on repeated administration by inducing desensitization of somatodendritic 5-HT 1A autoreceptors in the raphe nuclei and nerve terminal 5-HT 1B autoreceptors, which also mediate feedback inhibition of 5-HT release. These effects would lead to a slow increase in 5-HT levels which corresponds to the delayed clinical effect of the drugs. Evidence for subsensitivity of somatodendritic 5-HT 1A autoreceptors after chronic administration of SSRIs has been provided by microdialysis experiments in which 5-HT levels are measured in vivo in response to a challenge dose of the 5-HT 1A receptor agonist, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) (Rutter et al. 1994, Kreiss andLucki 1995;Invernizzi et al. 1994). However, other studies using SSRIs (Hjorth and Auerbach 1994; Bosker et al. 1995a,b;Invernizzi et al. 1995Invernizzi et al. , 1996 or clomipramine (Gur et al. 1999) failed to show any change in 5-HT 1A autoreceptor subsensitivity by this method. An increase in basal 5-HT levels after chronic SSRI administration, taken to be due to pre-synaptic 5-HT 1A and 5-HT 1B receptor desensitization, has been observed in cortex (Bel and Artigas 1993), hippocampus (Auerbach and Hjorth 1995) diencephalon (Rutter et al. 1994) an...

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Section: Serotonergic Receptors Of the 5-ht 1a Subtype Have Been Suggmentioning

confidence: 68%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Neuropsychopharmacology

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“…These diverse phenomena are also observed for serotonin 5-HT 2 receptors. Serotonin 5-HT 2 receptors are down-regulated after repeated treatment with citalopram, imipramine, and mianserin (Butler et al, 1993;Klimek et al, 1994), not changed following amitriptyline treatment (Cadogan et al, 1993), and up-regulated following levoprotiline, fluoxetine, and electroconvulsive shock treatment (Butler et al, 1993;Hrdina and Vu, 1993;Klimek et al, 1994). Adaptation of ␤-adrenergic or serotonergic receptors may not be the ultimate answer to the mechanism of action of antidepressants.…”

Section: Discussionmentioning

confidence: 99%

Effects of Repeated Antidepressant Treatment on Type 4A Phosphodiesterase (PDE4A) in Rat Brain

Jackson

O’Donnell

2000

Journal of Neurochemistry

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In a previous study, an up-regulation of rolipram-sensitive, low-K m , cyclic AMP phosphodiesterase (PDE4) subtype PDE4A in rat cerebral cortex following repeated treatment of desipramine was observed. To determine whether this effect is shared by antidepressants from different pharmacological classes, PDE4A expression was examined using immunoblot analyses following repeated treatment with the norepinephrine reuptake inhibitor desipramine, the monoamine oxidase inhibitor phenelzine, the atypical antidepressant trazodone, and the serotonin reuptake inhibitor fluoxetine. Desipramine, phenelzine, and fluoxetine all increased the intensities of the PDE4A bands in hippocampal preparations; trazodone did not. In preparations of cerebral cortex, the intensities of the PDE4A bands were increased following desipramine treatment, not changed following phenelzine or fluoxetine treatment, and decreased following trazodone treatment. It appears that repeated treatment with antidepressant drugs from different pharmacological classes produces similar effects on the expressions of PDE4A variants in hippocampus. This effect is not correlated with the changes in ␤-adrenergic receptor densities, suggesting these antidepressants may at some point alter intracellular signal transduction pathways in a similar manner.

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“…Additionally, serotonin-selective uptake inhibitors (SSRIs) have varying effects on 5-HT 2A down-regulation. For instance, depending on the study, fluoxetine has been reported to have either no effect on 5-HT 2A receptor number [15,40,41,76], or actually increase receptor number [52]. Similarly, paroxetine has also been reported to increase [15] or have no effect [3] on 5-HT 2A receptor numbers.…”

Section: Paradoxical Down-regulation Of 5-ht 2a By Antagonistsmentioning

confidence: 99%

“…Similarly, paroxetine has also been reported to increase [15] or have no effect [3] on 5-HT 2A receptor numbers. By contrast, citalopram has been shown to down-regulate 5-HT 2A [52,58]. It is likely that 5-HT2A receptor down-regulation is only one mode by which antidepressant drugs exert their therapeutic effects and that other downstream events are also involved in antidepressant drug action.…”

Section: Paradoxical Down-regulation Of 5-ht 2a By Antagonistsmentioning

confidence: 99%

Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists

Gray

Roth

2001

Brain Research Bulletin

264

205

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Effects of Repeated Treatment With Fluoxetine and Citalopram, a 5-Ht Uptake Inhibitors on 5-Ht1a and 5-Ht2 Receptors in the Rat Brain.

Cited by 34 publications

References 17 publications

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Effects of Repeated Antidepressant Treatment on Type 4A Phosphodiesterase (PDE4A) in Rat Brain

Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists

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