WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion

WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin... Previous studies suggest that the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n -propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin, adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin. However, the lack of selective 5-HT 1A receptor antagonists made it difficult to confirm that 5-HT 1A receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT 1A receptor antagonist, N -(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)- N -(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT 1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μ g/kg s.c., increased plasma levels of oxytocin (to 970% above basal levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal levels) and prolactin (to 313% above basal levels), but not renin. The lowest dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1 mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and maximally inhibited the corticosterone response to 8-OH-DPAT, although corticosterone levels were still above basal. In contrast, the increase in prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY-100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin levels were markedly elevated (1550%) and administration of 8-OH-DPAT significantly elevated plasma renin concentration. Taken together, these data indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but not prolactin secretion via activation of 5-HT 1A receptors and (2) blockade of 5-HT 1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT 1A receptor mechanisms. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

WAY-100635 inhibits 8-OH-DPAT-stimulated oxytocin, ACTH and corticosterone, but not prolactin secretion

Loading next page...
 
/lp/elsevier/way-100635-inhibits-8-oh-dpat-stimulated-oxytocin-acth-and-Z0szIT3V4e
Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science B.V.
ISSN
0014-2999
DOI
10.1016/S0014-2999(97)01607-5
Publisher site
See Article on Publisher Site

Abstract

Previous studies suggest that the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n -propylamino) tetralin (8-OH-DPAT) increases the secretion of oxytocin, adrenocorticotropic hormone (ACTH), corticosterone and prolactin but not renin. However, the lack of selective 5-HT 1A receptor antagonists made it difficult to confirm that 5-HT 1A receptors mediate the neuroendocrine responses to 8-OH-DPAT. This study investigated the effects of increasing doses of a selective 5-HT 1A receptor antagonist, N -(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)- N -(2-pyridinyl) cyclohexanecarboxamide (WAY-100635) on neuroendocrine responses induced by the 5-HT 1A receptor agonist 8-OH-DPAT in adult male rats. 8-OH-DPAT, 500 μ g/kg s.c., increased plasma levels of oxytocin (to 970% above basal levels); ACTH (to 1622% above basal levels), corticosterone (to 458% above basal levels) and prolactin (to 313% above basal levels), but not renin. The lowest dose of WAY-100635 (0.1 mg/kg s.c.) significantly inhibited the 8-OH-DPAT-induced increase in plasma oxytocin but not ACTH or corticosterone levels. At a dose of 1 mg/kg (s.c.), WAY-100635 completely blocked the oxytocin and ACTH responses and maximally inhibited the corticosterone response to 8-OH-DPAT, although corticosterone levels were still above basal. In contrast, the increase in prolactin secretion, induced by 8-OH-DPAT was not inhibited by any dose of WAY-100635. At the highest dose of WAY-100635 (10 mg/kg, s.c.), basal prolactin levels were markedly elevated (1550%) and administration of 8-OH-DPAT significantly elevated plasma renin concentration. Taken together, these data indicate that: (1) 8-OH-DPAT stimulates oxytocin, ACTH, and corticosterone but not prolactin secretion via activation of 5-HT 1A receptors and (2) blockade of 5-HT 1A receptors may unmask 8-OH-DPAT simulation of renin secretion via non-5-HT 1A receptor mechanisms.

Journal

European Journal of PharmacologyElsevier

Published: Apr 10, 1998

References

  • A pharmacological profile of the selective silent 5-HT 1A receptor antagonist, WAY-100635
    Forster, E.A.; Cliffe, I.A.; Bill, D.J.; Dover, G.M.; Jones, D.; Reilly, Y.; Fletcher, A.
  • The 5-HT 1A receptor is not involved in emotional stress-induced rises in stress hormones
    Groenink, L.; Mos, J.; Van der Gugten, J.; Olivier, B.
  • 8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: Evidence for a role of both 5-HT 1A and dopamine D 1 receptors
    Hajós-Korcsok, E.; Sharp, T.
  • 8-OH-DPAT-induced hypotensive action and sympathoexcitatory neurons in the rostral ventrolateral medulla of the rat
    Kubo, T.; Taguchi, K.; Ozaki, S.; Amano, M.; Ishizuka, T.
  • Neuroendocrine profile of the potential anxiolytic drug S-20499
    Levy, A.D.; Li, Q.; Gustafson, M.; Van de Kar, L.D.
  • Autoradiographic evidence for differential G-protein coupling of 5-HT 1A receptors in the rat brain: Lack of effect by repeated injections of fluoxetine
    Li, Q.; Battaglia, G.; Van de Kar, L.D.

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