Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat

I. Lucki, M. S. Nobler, Alan Frazer

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Abstract

Ligand binding studies have identified certain serotonin (5-HT) antagonists with selective affinity for 5-HT2 receptors and other serotonin antagonists with affinity for both 5-HT1 and 5-HT2 receptors. This study compared the actions of ketanserin and pipamperone, selective 5-HT2 receptor antagonists, with metergoline and methylsergide, nonselective 5-HT antagonists, on two behavioral response in rats that are produced by the activation of 5-HT receptors: 1) the head shake response and 2) the 5-HT syndrome. Both the selective and the nonselective 5-HT antagonists blocked the head shake response produced by 5-hydroxy-L-tryptophan. The order of relative potency was: metergoline > ketanserin > pipamperone > methysergide. All four antagonists also blocked the head shake response produced by the 5-HT agonist quipazine. In contrast, the symptoms of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine were blocked by pretreatment with the nonselective 5-HT receptor antagonists but not by the 5-HT2 receptor antagonists. The differential actions of 5-HT antagonists on these behavioral responses suggest that different 5-HT receptors are involved in the head shake response and the 5-HT syndrome. That the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5-HT2 receptor suggests that the 5-HT2 receptor is involved in the head shake response. In contrast, the ability of 5-HT antagonists with affinity for the 5-HT1 receptor to block the 5-HT syndrome and the inability of 5-HT2 receptor antagonists to block the syndrome suggests that this behavioral response probably involves the activation of 5-HT1 receptors.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume228
Issue number1
StatePublished - 1984
Externally publishedYes

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Serotonin Antagonists
Serotonin Receptors
Serotonin 5-HT2 Receptor Antagonists
Head
Serotonin 5-HT1 Receptors
pipamperone
Serotonin
Metergoline
Ketanserin
Methoxydimethyltryptamines
Quipazine
Methysergide
5-Hydroxytryptophan
Serotonin Receptor Agonists
Tryptophan
Ligands
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

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abstract = "Ligand binding studies have identified certain serotonin (5-HT) antagonists with selective affinity for 5-HT2 receptors and other serotonin antagonists with affinity for both 5-HT1 and 5-HT2 receptors. This study compared the actions of ketanserin and pipamperone, selective 5-HT2 receptor antagonists, with metergoline and methylsergide, nonselective 5-HT antagonists, on two behavioral response in rats that are produced by the activation of 5-HT receptors: 1) the head shake response and 2) the 5-HT syndrome. Both the selective and the nonselective 5-HT antagonists blocked the head shake response produced by 5-hydroxy-L-tryptophan. The order of relative potency was: metergoline > ketanserin > pipamperone > methysergide. All four antagonists also blocked the head shake response produced by the 5-HT agonist quipazine. In contrast, the symptoms of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine were blocked by pretreatment with the nonselective 5-HT receptor antagonists but not by the 5-HT2 receptor antagonists. The differential actions of 5-HT antagonists on these behavioral responses suggest that different 5-HT receptors are involved in the head shake response and the 5-HT syndrome. That the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5-HT2 receptor suggests that the 5-HT2 receptor is involved in the head shake response. In contrast, the ability of 5-HT antagonists with affinity for the 5-HT1 receptor to block the 5-HT syndrome and the inability of 5-HT2 receptor antagonists to block the syndrome suggests that this behavioral response probably involves the activation of 5-HT1 receptors.",
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T1 - Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat

AU - Lucki, I.

AU - Nobler, M. S.

AU - Frazer, Alan

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