Antidepressant-like Effects of a Partial Agonist at Strychnine-insensitive Glycine Receptors and a Competitive NMDA Receptor Antagonist

The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration

“…The hippocampus may mediate the effects of compounds with diverse mechanisms of action in preclinical models of anxiety and depression. For example, the reduced immobility in the forced swim test in rats has been observed after intrahippocampal administration of tricyclic antidepressants, imipramine (Przegalinski et al 1997), and desipramine (Kostowski 1985); 5-HT7 receptor antagonists (Wesolowska et al 2006); ionotropic glutamate receptor antagonist (Padovan and Guimaraes 2004); as well as neurotrophic factors (Shirayama et al 2002). Moreover, the hippocampus mediates the effects of benzodiazepines or a direct GABAA receptor agonist (Menard and Treit 2001;Rezayat et al 2005), serotonin receptor (i.e., 5-HT1A and 5-HT7) ligands (Menard and Treit 1998;Wesolowska et al 2006), an acetylcholinesterase inhibitor (Degroot and Treit 2002), ionotropic or metabotropic glutamate receptor ligands (Padovan et al 2000;Palucha et al 2004), and neurosteroids (Bitran et al 1999) in various models of anxiety, including the conflict drinking test and the elevated plus maze test.…”

Antidepressant mechanisms: functional and molecular correlates of excitatory amino acid neurotransmission

“…34,47 Both competitive and non-competitive NMDA receptor antagonists are active in the forced swimming test [77][78][79] and the learned helplessness model. 80 However, the relationship between NMDA blockade and antidepressant action is not clear-cut; in certain cases NMDA receptor antagonists can inhibit the action of clinically effective antidepressant treatments.…”

Is Ro 61-8048 a potential fast-acting antidepressant?

“…Inescapable stressors that serve as animal models of depression were shown to reduce NMDA receptor dependent long-term potentiation [14]. Contrarily, NMDA receptor blockers were shown to reduce immobilisation that mice display in forced swim test in a similar extent than antidepressant acting on the monoamine system [15]: similar effects were found in other depression models [16][17][18]. According to these experimental data human trials also suggested the effectiveness of NMDA blockers.…”