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

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
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

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