Antisense Inhibition of 5-Hydroxytryptamine<sub>2a</sub>Receptor Induces an Antidepressant-Like Effect in Mice

Sibille, Etienne; Sarnyai, Zoltán; Benjamin, Daniel; Gál, Judit; Baker, Harriet; Tóth, Miklós

doi:10.1124/mol.52.6.1056

Cited by 71 publications

(32 citation statements)

References 34 publications

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“…Preclinical and clinical studies have shown that 5-HT 1A receptor agonists have antidepressant activity [56,57] . Intracerebroventricular injection of mRNA antisense to 5-HT 2A receptors or systemic injection of a selective 5-HT 2A receptor antagonist produces antidepressant effects in rodent models [58,59] . Agomelatine, a potent melatonin receptor agonist, also acts as an antagonist at 5-HT 2C receptors and exerts antidepressant activities in several animal models [23][24][25]31] .…”

Section: Discussionmentioning

confidence: 99%

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

et al. 2010

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Aim: To investigate the potential antidepressant and anxiolytic effects of Neu-P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. Methods: In the learned helplessness test (LH), Neu-P11 or melatonin (25-100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for 5 days and the number of escape failures and intertrial crossings during the test phase were recorded. In the forced swimming test (FST), rats received a single or repeated administration of Neu-P11 (25-100 mg/kg, ip). The total period of immobility during the test phase was assessed. In the elevated plus-maze test (EPM), mice were treated with Neu-P11 (25-100 mg/kg, ip) or melatonin in the morning or in the evening and tested 2 h later. The percentage of time spent in the open arms and the open arms entries were assessed. Results: In the LH test, Neu-P11 but not melatonin significantly decreased the escape deficit and had no effect on the intertrial crossings. In the FST, a single or repeated administration of Neu-P11, either in the morning or in the evening, significantly decreased the duration of immobility. In the EPM test, Neu-P11 significantly increased the percentage of time spent in the open arms and the open arms entries irrespective to the time of administration. Melatonin was effective only when administered in the afternoon. Conclusion:The results demonstrate that Neu-P11 exerts antidepressant and anxiolytic activities in rodent models.

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Section: Discussionmentioning

confidence: 99%

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

et al. 2010

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“…The stability of mRNA and unmodified oligos in brain (Jirikowski et al, 1992;Yee et al, 1994) and the effectiveness of unmodified antisense oligos injected intracerebroventricularly (Wahlestedt et al, 1993a,b;Sibille et al, 1997) are consistent with the low activity of nucleases in brain. In the current study, we may have not observed a decrease in cortical 5-HT2A receptors following antisense oligo infusion because the activity of RNase H in adult rat brain is not sufficient to support the inhibition of protein expression by an antisense oligo targeting the coding region of mRNA.…”

Section: Figmentioning

confidence: 73%

“…In the current study, we may have not observed a decrease in cortical 5-HT2A receptors following antisense oligo infusion because the activity of RNase H in adult rat brain is not sufficient to support the inhibition of protein expression by an antisense oligo targeting the coding region of mRNA. Very recently the down-regulation of 5-HT2A receptors in cortex and striatum has been reported following injection of an antisense oligo intracerebroventricularly for 4 days (Sibille et al, 1997). Although this antisense oligo corresponds to the coding region of 5-HT2A receptor mRNA, the target sequence (+10 to +27) (Julius et al, 1990) may be sufficiently close to the translation initiation codon to block translation initiation.…”

Section: Figmentioning

confidence: 99%

Regulation of Serotonin_2A Receptor Expression by an Antisense Oligodeoxynucleotide

Scalzitti

Berg

Kratowicz

et al. 1998

Journal of Neurochemistry

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Abstract:The regulation of 5-HT2A receptor expression by an antisense oligodeoxynucleotide, complementary to the coding region of rat 5-HT2A receptor mRNA, was examined in a cortically derived cell line and in rat brain. Treatment of A1A1 variant cells, which express the 5-HT2A receptor coupled to the stimulation of phosphatidylinositol (P1) hydrolysis, with antisense oligodeoxynucleotide decreased the maximal stimulation of P1 hydrolysis by the partial agonist quipazine and the number of 5-HT2A receptor sites as measured by the binding of 2~[125l]ĩ odolysergic acid diethylamide. Treatment of cells with random, sense, or mismatch oligodeoxynucleotide did not alter the stimulation of P1 hydrolysis by quipazine or 5-HT2A receptor number. Intracerebroventricular infusion of antisense, but not mismatch, oligodeoxynucleotide for 8 days resulted in a significant increase in cortical 5-HT2A receptor density and an increase in headshake behavior induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. The density of cortical 5-HT2A receptors was not altered by administration of antisense oligodeoxynucleotide for 1, 2, or 4 days. We hypothesize that in brain this antisense oligodeoxynucleotide relieved some form of translational suppression, resulting in an increase in 5-HT2A receptor expression. Key Words: 5-HT2A receptors-A1A1 variant cellsPhosphoinositide hydrolysis-Headshake behavior-Intracerebroventricular infusion. J. Neurochem. 71, 1457Neurochem. 71, -1463Neurochem. 71, (1998.Pharmacological, functional, as well as molecular criteria have contributed to the characterization of many subtypes of receptor for the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT). The 5-HT2A receptor is found in high density in cortex, where it is enriched on pyramidal neurons Jakab and Goldman-Rakic, 1998), and in intermediate density in hypothalamus, caudate putamen, and nucleus accumbens (see Hoyer et al., 1994). 5-HT2A receptors have been implicated in a wide variety of behavioral and physiological processes as well as in the mechanism of action of psychotropic drugs. The 5-HT2A receptor appears to be the site of action of hallucinogenic compounds and has high affinity for atypical neuroleptics and many antidepressant drugs (Glennon, 1990;Leysen et al., 1993;Frazer, 1997).We have studied the regulation of expression of the 5-HT2A receptor by an antisense oligodeoxynucleotide (oligo) using a cortically derived cell line, A1A1 variant (AtAtv) cells, and in brain following intracerebroventricular infusion. A~A~v cells express 5-HT2A receptors coupled to the stimulation of phosphatidylinositol (P1) hydrolysis (Berg et al., 1994a). An antisense oligo designed to hybridize to the coding region of 5-HT2A receptor mRNA was used in these studies. MATERIALS AND METHODS OligosOligos, corresponding to coding region +57 to +74 (Julius et al., 1990) of rat 5-HT2A receptor cDNA (accession no. M30705), were used (5'to 3'): antisense, GGGCCA-TCACCTAATTGC; sense, GCAATTAGGTGATGGCCC; random, CCTCGTAATGCAGACTCG; mi...

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“…Additionally, the reduction of the 5-HT 2A receptors by the administration of antisense oligonucleotide produced an antidepressant-like effect in the forced swim test in mice [69]. Recently, several studies have suggested that the addition of drugs with significant 5-HT 2A antagonist properties, such as atypical antipsychotic dugs or antidepressants (e.g., mianserin and mirtazapine), to SSRIs enhance therapeutic responses in major depression [43,17].…”

Section: Discussionmentioning

confidence: 99%

5-HT2A receptor antagonist M100907 reduces serotonin synthesis: An autoradiographic study

Hasegawa

Fikre-Merid

Dikšić

2012

Brain Research Bulletin

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The effects of the administration of the serotonin (5-HT) 2A antagonist, M100907, on 5-HT synthesis rates, were evaluated using the α-[ 14 C]methyl-L-tryptophan (α-MTrp) autoradiographic method. In the treatment study, M100907 (10 mg/kg) was injected intraperitoneally 30 min before the α-MTrp injection (30 μCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus.These data suggest that the terminal 5-HT 2A receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT 2A antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens.

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Antisense Inhibition of 5-Hydroxytryptamine_2aReceptor Induces an Antidepressant-Like Effect in Mice

Cited by 71 publications

References 34 publications

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

Regulation of Serotonin_2A Receptor Expression by an Antisense Oligodeoxynucleotide

5-HT2A receptor antagonist M100907 reduces serotonin synthesis: An autoradiographic study

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Antisense Inhibition of 5-Hydroxytryptamine2aReceptor Induces an Antidepressant-Like Effect in Mice

Cited by 71 publications

References 34 publications

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

Regulation of Serotonin2A Receptor Expression by an Antisense Oligodeoxynucleotide

5-HT2A receptor antagonist M100907 reduces serotonin synthesis: An autoradiographic study

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Antisense Inhibition of 5-Hydroxytryptamine_2aReceptor Induces an Antidepressant-Like Effect in Mice

Regulation of Serotonin_2A Receptor Expression by an Antisense Oligodeoxynucleotide