Differential Regulation of Somatodendritic Serotonin 5‐HT1A Receptors by 2‐Week Treatments with the Selective Agonists Alnespirone (S‐20499) and 8‐Hydroxy‐2‐(Di‐n‐Propylamino)tetralin

Differential Regulation of Somatodendritic Serotonin 5‐HT1A Receptors by 2‐Week Treatments... Abstract : Single treatment with the serotonin (5‐hydroxytryptamine) 5‐HT1A receptor agonists 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) and alnespirone (S‐20499) reduces the extracellular 5‐HT concentration (5‐HText) in the rat midbrain and forebrain. Given the therapeutic potential of selective 5‐HT1A agonists in the treatment of affective disorders, we have examined the changes in 5‐HT1A receptors induced by 2‐week minipump administration of alnespirone (0.3 and 3 mg/kg/day) and 8‐OH‐DPAT (0.1 and 0.3 mg/kg/day). The treatment with alnespirone did not modify baseline 5‐HText but significantly attenuated the ability of 0.3 mg/kg s.c. alnespirone to reduce 5‐HText in the dorsal raphe nucleus (DRN) and frontal cortex. In contrast, the ability of 8‐OH‐DPAT (0.025 and 0.1 mg/kg s.c.) to reduce 5‐HText in both areas was unchanged by 8‐OH‐DPAT pretreatment. Autoradiographic analysis revealed a significant reduction of [3H]8‐OH‐DPAT and [3H]WAY‐100635 {3H‐labeled N‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridyl)cyclohexanecarboxamide · 3HCl} binding to somatodendritic 5‐HT1A receptors (but not to postsynaptic 5‐HT1A receptors) of rats pretreated with alnespirone but not with 8‐OH‐DPAT. In situ hybridization analysis revealed no change of the density of the mRNA encoding the 5‐HT1A receptors in the DRN after either treatment. These data indicate that continuous treatment for 2 weeks with alnespirone, but not with 8‐OH‐DPAT, causes a functional desensitization of somatodendritic 5‐HT1A receptors controlling 5‐HT release in the DRN and frontal cortex. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Differential Regulation of Somatodendritic Serotonin 5‐HT1A Receptors by 2‐Week Treatments with the Selective Agonists Alnespirone (S‐20499) and 8‐Hydroxy‐2‐(Di‐n‐Propylamino)tetralin

Loading next page...
 
/lp/wiley/differential-regulation-of-somatodendritic-serotonin-5-ht1a-receptors-0Nx0lnqhyt
Publisher
Wiley
Copyright
© International Society for Neurochemistry
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1046/j.1471-4159.1999.0720262.x
Publisher site
See Article on Publisher Site

Abstract

Abstract : Single treatment with the serotonin (5‐hydroxytryptamine) 5‐HT1A receptor agonists 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) and alnespirone (S‐20499) reduces the extracellular 5‐HT concentration (5‐HText) in the rat midbrain and forebrain. Given the therapeutic potential of selective 5‐HT1A agonists in the treatment of affective disorders, we have examined the changes in 5‐HT1A receptors induced by 2‐week minipump administration of alnespirone (0.3 and 3 mg/kg/day) and 8‐OH‐DPAT (0.1 and 0.3 mg/kg/day). The treatment with alnespirone did not modify baseline 5‐HText but significantly attenuated the ability of 0.3 mg/kg s.c. alnespirone to reduce 5‐HText in the dorsal raphe nucleus (DRN) and frontal cortex. In contrast, the ability of 8‐OH‐DPAT (0.025 and 0.1 mg/kg s.c.) to reduce 5‐HText in both areas was unchanged by 8‐OH‐DPAT pretreatment. Autoradiographic analysis revealed a significant reduction of [3H]8‐OH‐DPAT and [3H]WAY‐100635 {3H‐labeled N‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridyl)cyclohexanecarboxamide · 3HCl} binding to somatodendritic 5‐HT1A receptors (but not to postsynaptic 5‐HT1A receptors) of rats pretreated with alnespirone but not with 8‐OH‐DPAT. In situ hybridization analysis revealed no change of the density of the mRNA encoding the 5‐HT1A receptors in the DRN after either treatment. These data indicate that continuous treatment for 2 weeks with alnespirone, but not with 8‐OH‐DPAT, causes a functional desensitization of somatodendritic 5‐HT1A receptors controlling 5‐HT release in the DRN and frontal cortex.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1999

Keywords: ; ; ; ; ;

References

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 lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off