Mianserin‐induced 5‐HT 2 receptor downregulation results in anxiolytic effects in the elevated plus‐maze test

Mianserin‐induced 5‐HT 2 receptor downregulation results in anxiolytic effects in the... Several agents that downregulate 5‐HT2 receptors produce anxiolytic effects in humans, but the role of 5‐HT2 receptor downregulation has been difficult to assess because of their other actions. To test the effects of pharmacological downregulation of 5‐HT2 receptors on exploratory behavior in the mouse, mianserin, a drug known to downregulate 5‐HT2 receptors after a single dose, was administered 30 min, 48 hr, or 18 days prior to testing in the elevated plus‐maze. Following testing in the elevated maze, the head‐shake response to 4‐iodo‐R‐(—)‐2,5‐dimethoxyphenylisopropylamine (DOI), a selective 5‐HT2/5‐HT1C agonist was assessed, and in a separate group of animals 5‐HT1A, 5‐HT1B, 5‐HT1C, β1,β2, and 5‐HT2 agonist and antagonist binding was quantified autoradiographically. Mianserin pretreatment resulted in a significant dose‐related anxiolytic effect in the elevated plus maze evidenced by increases in the percentage of entries to, and time spent on the open arms. Head‐shakes induced by DOI were also dose‐dependently decreased as a result of mianserin pretreatment. At this time, the binding of the 5‐HT2 receptor antagonist, 7‐amino‐8(125I)ketanserin was decreased by 50%. Binding of DOI to 5‐HT2 receptors was decreased by 46%, and to 5‐HT1C receptors was decreased by 53%, but no other changes were found in any of the other receptor types examined. These findings demonstrate that the 5‐HT2 receptor plays at least a permissive role in anxiety‐like behaviors, since an intact 5‐HT2 system is necessary for the full expression of the anxiety‐like response, but the role of 5‐HT1C receptor downregulation in the effects of mianserin cannot be ruled out at this time. © 1992 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Development Research Wiley

Mianserin‐induced 5‐HT 2 receptor downregulation results in anxiolytic effects in the elevated plus‐maze test

Loading next page...
 
/lp/wiley/mianserin-induced-5-ht-2-receptor-downregulation-results-in-anxiolytic-UrFXWc1xXo
Publisher
Wiley
Copyright
Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company
ISSN
0272-4391
eISSN
1098-2299
DOI
10.1002/ddr.430260308
Publisher site
See Article on Publisher Site

Abstract

Several agents that downregulate 5‐HT2 receptors produce anxiolytic effects in humans, but the role of 5‐HT2 receptor downregulation has been difficult to assess because of their other actions. To test the effects of pharmacological downregulation of 5‐HT2 receptors on exploratory behavior in the mouse, mianserin, a drug known to downregulate 5‐HT2 receptors after a single dose, was administered 30 min, 48 hr, or 18 days prior to testing in the elevated plus‐maze. Following testing in the elevated maze, the head‐shake response to 4‐iodo‐R‐(—)‐2,5‐dimethoxyphenylisopropylamine (DOI), a selective 5‐HT2/5‐HT1C agonist was assessed, and in a separate group of animals 5‐HT1A, 5‐HT1B, 5‐HT1C, β1,β2, and 5‐HT2 agonist and antagonist binding was quantified autoradiographically. Mianserin pretreatment resulted in a significant dose‐related anxiolytic effect in the elevated plus maze evidenced by increases in the percentage of entries to, and time spent on the open arms. Head‐shakes induced by DOI were also dose‐dependently decreased as a result of mianserin pretreatment. At this time, the binding of the 5‐HT2 receptor antagonist, 7‐amino‐8(125I)ketanserin was decreased by 50%. Binding of DOI to 5‐HT2 receptors was decreased by 46%, and to 5‐HT1C receptors was decreased by 53%, but no other changes were found in any of the other receptor types examined. These findings demonstrate that the 5‐HT2 receptor plays at least a permissive role in anxiety‐like behaviors, since an intact 5‐HT2 system is necessary for the full expression of the anxiety‐like response, but the role of 5‐HT1C receptor downregulation in the effects of mianserin cannot be ruled out at this time. © 1992 Wiley‐Liss, Inc.

Journal

Drug Development ResearchWiley

Published: Jan 1, 1992

Keywords: serotonin; anxiety; 5‐HT 1C ; receptors; autoradiography

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off