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

The aim of the present paper was to study the effects of GABA(A) receptor-positive modulators (L-838417 and NS11394) showing a preference for alpha 2/3 subunits of the GABA(A) 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. Behavioural Pharmacology 23: 790-801 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.