Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats

This study describes the effects of intra-lateral septal infusions of different doses of the mGluR5 antagonist MTEP in the DRL-72 s paradigm and the elevated plus-maze test in rats, two behavioral models known to be sensitive to antidepressant-like and anxiolytic-like drug effects, respectively. Intra-lateral septal infusions of MTEP induced a dose-dependent (5.0 mu g/mu l, P < 0.05; 10.0 mu g/mu l, P < 0.05) increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution (5.0 mu g/mu l, P < 0.05; 10.0 mu g/mu l, P < 0.05). These effects are indicative of antidepressant-like actions of the compound. Desipramine, a prototypical antidepressant drug, induced (5.0 mu g/mu l; P < 0.05) similar effects. In the elevated plus-maze test, intra-lateral septal infusions of MTEP (5.0 mu g/mu l, P < 0.05; 10.0 mu g/mu l, P < 0.05) increased e exploration of the open arms without affecting locomotion. This anxiolytic-like effect was similar to that observed with the infusion of the benzodiazepine midazolam (10.0 mu g/mu l; P < 0.05) in the same brain area. It is concluded that intra-lateral septal infusions of the mGlu5 receptor antagonist MTEP produced antidepressant-like actions or anxiolytic-like effects in male rats. (c) 2006 Elsevier Inc. All rights reserved.