Chronic mianserin treatment decreases 5-HT2 receptor binding without altering 5-HT2 receptor mRNA levels

doi:10.1016/0922-4106(91)90093-W

European Journal of Pharmacology: Molecular Pharmacology

Volume 207, Issue 2, 19 June 1991, Pages 169-172

https://doi.org/10.1016/0922-4106(91)90093-W Get rights and content

Abstract

Rats were injected with 15 mg/kg (i.p.) mianserin or vehicle (saline) for 4, 10 or 21 days and 5-HT₂ receptor binding and mRNA levels measured. Treatment with mianserin induced a substantial decrease in 5-HT₂ radioligand binding (44–59% decrease; P < 0.05 vs. control). No changes in the amount of 5-HT₂ or, as a control, β-actin mRNAs were found (P > 0.05 vs. control). These results indicate that mianserin decreases 5-HT₂ radioligand binding without altering steady-state 5-HT₂ mRNA levels.

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For more than 30 years it has been known that some antagonists can down-regulate cortical 5-HT2A radioligand binding in vivo (Bergstrom and Kellar, 1979; Peroutka and Snyder, 1980)—a finding which has been widely replicated see (Gray and Roth, 2001) for review. Such ’down-regulation’ of 5-HT2A receptors occurs without changes in 5-HT2A mRNA (Roth et al., 1990; Roth and Ciaranello, 1991) and is accompanied by apparent 5-HT2A receptor internalization (Willins et al., 1999). Selected antipsychotic and antidepressant drugs can induce a decrease in 5-HT2A radioligand binding after chronic administration (Bergstrom and Kellar, 1979; Peroutka and Snyder, 1980; Mikuni and Meltzer, 1984; Andree et al., 1986), although this is not a characteristic of all drugs in these classes (Brunello et al., 1982; Barbaccia et al., 1983).
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The effect of ligand pretreatment on human 5-hydroxytryptamine_2C (5-HT_2C) receptors was examined in CHO cells expressing high (CHO-1C7; 67±3 pmol/mg) or low (CHO-1C19; 72±10 fmol/mg) levels of the receptor. Seventy-two hours pretreatment of CHO-1C7 cells with various ligands did not affect receptor expression. Pretreatment with inverse agonists enhanced 5-HT-mediated inositol phosphate accumulation with no change in constitutive receptor activity. The enhanced agonist responsiveness was inversely correlated with the intrinsic activity of the pretreatment ligand. Seventy-two hours of pretreatment with the weak agonist, 5-methoxygramine, caused an elevation in constitutive activity but no alteration in 5-HT-mediated signaling. In CHO-1C19 cells, 24 but not 72 h of pretreatment with the inverse agonist mianserin enhanced 5-HT-mediated signaling, with no effect on basal signaling; pretreatment with 5-methoxygramine had no significant effect. These findings highlight differences in the pattern of chronic regulation of 5HT_2C receptor signaling between high and low receptor expression levels in a common cellular background.
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Short communicationChronic mianserin treatment decreases 5-HT2 receptor binding without altering 5-HT2 receptor mRNA levels

Abstract

Anal. Biochem.

Serotonin receptor sensitivity after acute and chronic treatment with mianserin

J. Pharmacol. Exp. Ther.

Acute and chronic effects of serotonin antagonists on serotonin binding sites

N. S. Arch. Pharmacol.

Basic Methods in Molecular Biology

Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex

Life Sci.

Short communication
Chronic mianserin treatment decreases 5-HT₂ receptor binding without altering 5-HT₂ receptor mRNA levels