Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABAA receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function

Martine Hofmann, Krisztina Sz Kordás, Andreas Gravius, Kata Bölcskei, Chris G. Parsons, Andrzej Dekundy, Wojciech Danysz, László Dézsi, Ina M. Wittko-Schneider, Katalin Sághy, István Gyertyán, Csilla Horváth

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.

Original languageEnglish
Pages (from-to)790-801
Number of pages12
JournalBehavioural Pharmacology
Volume23
Issue number8
DOIs
Publication statusPublished - Dec 1 2012
Externally publishedYes

Keywords

  • GABAA
  • anxiety
  • learning
  • motor impairment
  • neuropathic pain
  • rat
  • side-effects
  • α2/3 selective

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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    Hofmann, M., Kordás, K. S., Gravius, A., Bölcskei, K., Parsons, C. G., Dekundy, A., Danysz, W., Dézsi, L., Wittko-Schneider, I. M., Sághy, K., Gyertyán, I., & Horváth, C. (2012). Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABAA receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function. Behavioural Pharmacology, 23(8), 790-801. https://doi.org/10.1097/FBP.0b013e32835a7c7e