HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats.

Abstract
Serotonin (5-HT)(1A) receptor agonists have been reported to produce mydriasis in mice, and miosis in rabbits and humans. However, the underlying mechanisms for this action are unclear. This study was undertaken in an attempt to explore the mechanism by which 5-HT(1A) receptors are involved in the modulation of pupillary size in pentobarbital-anesthetized rats. Intravenous administration of the 5-HT(1A) receptor agonist, (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.003-3 mg/kg), elicited dose-dependent pupillary dilation, which was not affected by section of the preganglionic cervical sympathetic nerve. 8-OH-DPAT-elicited mydriatic responses were attenuated by the selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate (WAY 100635; 0.3-1 mg/kg, i.v.), as well as by the selective alpha(2)-adrenoceptor antagonist, (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-dechydro-3-methoxy-12-(ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine hydrochloride (RS 79948; 0.3 mg/kg, i.v.), but not by the selective alpha(1)-adrenoceptor antagonist, prazosin (0.3 mg/kg, i.v.). Mydriatic responses elicited by the alpha(2)-adrenoceptor agonist, guanabenz (0.003-0.3 mg/kg, i.v.), were not antagonized by WAY 100635 (0.3-1 mg/kg, i.v.). To determine whether central nervous system (CNS) 5-HT(1A) receptors, like alpha(2)-adrenoceptors, are involved in reflex mydriasis, voltage response curves of pupillary dilation were constructed by stimulation of the sciatic nerve in anesthetized rats. WAY 100635 (1 mg/kg, i.v.) did not antagonize the evoked reflex mydriasis, which, however, was blocked by RS 79948 (0.3 mg/kg, i.v.). Taken together, these results suggest that 8-OH-DPAT produces pupillary dilation in anesthetized rats by stimulating CNS 5-HT(1A) receptors, which in turn trigger the release of norepinephrine, presumably from the locus coeruleus. The latter reduces parasympathetic neuronal tone to the iris sphincter muscle by stimulation of postsynaptic alpha(2)-adrenoceptors within the Edinger-Westphal nucleus. Unlike alpha(2)-adrenoceptors, 5-HT(1A) receptors in the CNS do not mediate reflex mydriasis evoked by sciatic nerve stimulation.
AuthorsYongxin Yu, Andrew G Ramage, Michael C Koss
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 489 Issue 3 Pg. 207-13 (Apr 12 2004) ISSN: 0014-2999 [Print] Netherlands
PMID15087245 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Adrenergic alpha-2 Receptor Antagonists
  • Isoquinolines
  • Naphthyridines
  • Piperazines
  • Pyridines
  • RS 79948-197
  • Receptors, Adrenergic, alpha-2
  • Serotonin 5-HT1 Receptor Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Guanabenz
Topics
  • 8-Hydroxy-2-(di-n-propylamino)tetralin (administration & dosage, antagonists & inhibitors, pharmacokinetics)
  • Adrenergic alpha-2 Receptor Antagonists
  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Guanabenz (pharmacology)
  • Injections, Intravenous
  • Isoquinolines (pharmacology)
  • Male
  • Mydriasis (chemically induced, prevention & control)
  • Naphthyridines (pharmacology)
  • Piperazines (pharmacology)
  • Pupil (drug effects, physiology)
  • Pyridines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A (administration & dosage, physiology)
  • Receptors, Adrenergic, alpha-2 (administration & dosage, physiology)
  • Sciatic Nerve (pathology, physiology)
  • Serotonin 5-HT1 Receptor Antagonists

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: