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

Pharmacology, Biochemistry, and Behavior
A R AllenI Lucki

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.

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Citations

Apr 24, 2007·Neurotoxicity Research·Neil E Paterson, Athina Markou
Jan 6, 2000·Progress in Neurobiology·C M PortasR Ursin
Apr 18, 2002·Neuroscience Letters·Nina K Popova, Elena A Ivanova
Sep 2, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·In-Jee YouSunmee Wee
Jul 12, 2005·Biochimica Et Biophysica Acta·Thomas J Pucadyil, Amitabha Chattopadhyay
Feb 5, 2003·Canadian Journal of Physiology and Pharmacology·Yoko Hagino, Masayuki Watanabe

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