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

Neuropharmacology
Karolina PodkowaAgnieszka Pałucha-Poniewiera

Abstract

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 d...Continue Reading

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Citations

Feb 13, 2019·The Journal of Pharmacology and Experimental Therapeutics·Mark H LewisAmber M Muehlmann
May 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaofei SheZhewen Dong

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