Volume 7 Supplement 2

13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)

Open Access

Neurokinin 1 receptor antagonism promotes active stress coping via enhanced septal 5-HT transmission

  • Georg M Singewald1,
  • Karl Ebner1,
  • Nigel Whittle1,
  • Francesco Ferraguti2 and
  • Nicolas Singewald2Email author
BMC Pharmacology20077(Suppl 2):A1

https://doi.org/10.1186/1471-2210-7-S2-A1

Published: 14 November 2007

Antagonists of the substance P (SP) preferring neurokinin 1 receptor (NK1-R) represent a promising novel class of drugs for the treatment of stress-related disorders including depression and anxiety disorders. The underlying neuronal mechanisms involved in the effects of these drugs, however, are poorly understood. By using in vivo microdialysis we observed increased SP, but reduced serotonin (5-HT) release during forced swim stress (FST) in the rat lateral septum (LS), a key area in processing emotions and stress responses. Acute administration of the selective high affinity NK1-R antagonist L-822429 injected either systemically or locally into the LS reversed the FST-induced decrease in 5-HT efflux and facilitated active coping strategies during the FST. Increased active coping in the FST was attenuated by intraseptal 5-HT1A-R blockade with WAY100635, indicating that the behavioural effect during NK1-R blockade is mediated by enhanced intraseptal serotonergic transmission acting on 5-HT1A-R. Taken together, our findings identify the LS as an important brain area for the modulation of stress responses by the SP/NK1-R system. NK1-R blockade resulted in behaviorally significant enhancement of 5-HT transmission. We show for the first time that this modulation does not necessarily involve interaction with neuronal firing at the cell body level of 5-HT neurons as previously postulated, but can be elicited in a terminal region of these neurons.

Authors’ Affiliations

(1)
Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck
(2)
Department of Pharmacology, Medical University of Innsbruck

Copyright

© Singewald et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

Advertisement