The 5-HT1A receptor antagonist p-MPPI blocks responses mediated by postsynaptic and presynaptic 5-HT1A receptors.

Abstract

The present experiments examined the ability of the novel 5-HT1A receptor antagonist to block responses mediated by postsynaptic and presynaptic 5-HT1A receptors in vivo. Pretreatment with p-MPPI reduced or blocked the effect of the 5-HT1A receptor agonist 8-OH-DPAT on two responses mediated by postsynaptic 5-HT1A receptors, reduction of body temperature and the 5-HT behavioral syndrome. Administration of p-MPPI alone did not alter body temperature or produce symptoms of the 5-HT syndrome. Pretreatment with p-MPPI also blocked the ability of 8-OH-DPAT to reduce extracellular 5-HT in the striatum, a response mediated by presynaptic 5-HT1A receptors in the dorsal raphe nucleus, but did not alter striatal 5-HT when administered alone. These results indicate that p-MPPI is an effective 5-HT1A receptor antagonist in vivo with no intrinsic activity. p-MPPI may prove to be a useful pharmacological tool for studying 5-HT1A receptors and their involvement in anxiety and affective disorders.

• Authors: A R Allen, A Singh, Z P Zhuang, M P Kung, H F Kung, I Lucki
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) 1997 May-Jun Vol. 57 Issue 1-2 Pg. 301-7 ISSN: 0091-3057 [Print] United States
• PMID: 9164586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aminopyridines
• Piperazines
• Serotonin Antagonists
• Serotonin Receptor Agonists
• 4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
• Serotonin
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Aminopyridines (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Body Temperature Regulation (drug effects)
• Corpus Striatum (drug effects, metabolism)
• Male
• Microdialysis
• Piperazines (pharmacology)
• Presynaptic Terminals (drug effects)
• Rats
• Rats, Sprague-Dawley
• Serotonin (metabolism)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)