The 5-HT1A receptor antagonist p-MPPI blocks 5-HT1A autoreceptors and increases dorsal raphe unit activity in awake cats

Bjørn Bjorvatn, Casimir A. Fornal, Francisco J. Martín, Christine W. Metzler, Barry L. Jacobs

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The effects of the putative 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (p-MPPI) were examined on the activity of serotonergic dorsal raphe nucleus neurons in freely moving cats. Systemic administration of p-MPPI produced a dose-dependent increase in firing rate. This stimulatory effect of p-MPPI was evident during wakefulness (when serotonergic neurons display a relatively high level of activity), but not during sleep (when serotonergic neurons display little or no spontaneous activity). p-MPPI also blocked the ability of the 5-HT1A receptor agonist 8-hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT) to inhibit serotonergic neuronal activity. This antagonism was evident both as a reversal of the neuronal inhibition produced by prior injection of 8-OH-DPAT and as a shift in the potency of 8-OH-DPAT following p-MPPI pretreatment. Overall, these results in behaving animals indicate that p-MPPI acts as an effective 5-HT1A autoreceptor antagonist. The increase in firing rate produced by p-MPPI supports the hypothesis that autoreceptor-mediated feedback inhibition operates under physiological conditions.

Original languageEnglish (US)
Pages (from-to)167-178
Number of pages12
JournalEuropean Journal of Pharmacology
Volume356
Issue number2-3
DOIs
StatePublished - Jan 1 1998

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • (Cat)
  • 5-HT (5-hydroxytryptamine, serotonin) neuron
  • 5-HT autoreceptor blockade
  • 5-HT receptor antagonist
  • Dorsal raphe nucleus
  • p-MPPI (4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide)

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