The potential antidepressant action and adverse effects profile of scopolamine co-administered with the mGlu7 receptor allosteric agonist AMN082 in mice

• Published in: Neuropharmacology 2018-10, Vol.141, p.214-222
• Main Authors: Podkowa, Karolina, Pilc, Andrzej, Podkowa, Adrian, Sałat, Kinga, Marciniak, Marcin, Pałucha-Poniewiera, Agnieszka
• Format: Article
• Language: English
• Subjects: Allosteric Regulation - drug effects; AMN082; Animals; Antidepressive Agents - administration & dosage; Antidepressive Agents - adverse effects; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - pharmacology; Depression; Drug Synergism; Excitatory Amino Acid Agonists - pharmacology; Forced swim test; Immobility Response, Tonic - drug effects; Locomotion - drug effects; Male; Maze Learning - drug effects; Metabotropic glutamate receptor; Mice; Mice, Knockout; Morris water maze; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - genetics; Rotarod Performance Test; Rotarod test; Scopolamine; Scopolamine - administration & dosage; Scopolamine - adverse effects; Scopolamine - pharmacology; Scopolamine - therapeutic use; Tail suspension test
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2018.08.022

Scopolamine, a muscarinic cholinergic receptor antagonist, exerts fast and prolonged antidepressant effects in the clinic. In contrast, the current treatments for major depressive disorder (MDD) require long-term drug administration. On the other hand, the sole use of scopolamine might be related to the high risk of adverse effects. Therefore, it may be preferable to reduce its therapeutic dose. A new approach might include the co-administration of low-dose scopolamine with selected ligands of metabotropic glutamate (mGlu) receptors, which are known to possess antidepressant-like activity in several rodent tests and models of depression. The aim of the present study was to evaluate the potential antidepressant activity of low-dose scopolamine combined with an allosteric agonist of mGlu7 receptors, AMN082 in C57BL/6 mice. It was found that the combination of scopolamine (0.1 mg/kg) and AMN082 (1 mg/kg) exerted significant antidepressant-like effects in the tail suspension test (TST), but these effects were not observed in the mGlu7−/− mice. Furthermore, low-dose AMN082 co-administered with low-doses scopolamine (0.03 and 0.1 mg/kg) induced antidepressant-like activity in the forced swim test (FST) in mice. The tested compounds did not affect locomotor activity and did not impair spatial memory in the Morris water maze (MWM) test or motor coordination in the rotarod test. The results strongly indicated that there is an enhanced antidepressant-like action of scopolamine by AMN082. Co-administration of scopolamine with AMN082 might be a new strategy with better efficacy and a lower risk of adverse effects compared with the sole use of scopolamine or AMN082. •AMN082 enhances the antidepressant-like effect of scopolamine in the TST and the FST in mice.•mGlu7 receptor is crucial in the antidepressant-like effect of jointly given scopolamine and AMN082.•Combined administration of scopolamine and AMN082 does not impair spatial memory in the Morris water maze.