Urotensin II acts as a modulator of mesopontine cholinergic neurons

Stewart D. Clark, Hans Peter Nothacker, Charles D. Blaha, Christopher J. Tyler, Dee M. Duangdao, Stephen L. Grupke, David R. Helton, Christopher S. Leonard, Olivier Civelli

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Urotensin II (UII) is a vasomodulatory peptide that was not predicted to elicit CNS activity. However, because we have recently shown that the urotensin II receptor (UII-R) is selectively expressed in rat mesopontine cholinergic (MPCh) neurons, we hypothesize that UII may have a central function. The present study demonstrates that the UII system is able to modulate MPCh neuron activity. Brain slice experiments demonstrate that UII excites MPCh neurons of the mouse laterodorsal tegmentum (LDTg) by activating a slow inward current. Furthermore, microinfusion of UII into the ventral tegmental area produces a sustained increase in dopamine efflux in the nucleus accumbens, as measured by in vivo chronoamperometry. In agreement with UII activation of MPCh neurons, intracerebroventricular injections of UII significantly modulate ambulatory movements in both rats and mice but do not significantly affect startle habituation or prepulse inhibition. The present study establishes that UII is a neuromodulator that may be exploited to target disorders involving MPCh dysfunction.

Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalBrain Research
Issue number2
StatePublished - Oct 19 2005

Bibliographical note

Funding Information:
We thank our colleagues Rainer Reinscheid, Steven Lin and Zhiwei Wang for advice during the course of this project. This work was supported by grants from NIH (MH60231 (OC), DK63001 (OC), HL64150 (CSL), NS27881 (CSL)) and from the Stanley Research Foundation (03R-415 (OC)).


  • Chronoamperometry
  • Electrophysiology
  • Locomotion
  • Mesopontine cholinergic
  • Prepulse inhibition
  • Urotensin II

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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