title: Antidepressant-like effects of scopolamine in mice are enhanced by the group II mGlu receptor antagonist LY341495.
abstract: Clinical studies have shown that the muscarinic receptor antagonist scopolamine induces a potent and rapid antidepressant effect relative to conventional antidepressants. However, potential undesirable effects, including memory impairment, partially limit the use of scopolamine in psychiatry. In the present study, we propose to overcome these limitations and enhance the therapeutic effects of scopolamine via administration in combination with the group II metabotropic glutamate (mGlu) receptor antagonist, LY341495. Joint administration of sub-effective doses of scopolamine (0.03 or 0.1 mg/kg, i.p.) with a sub-effective dose of LY341495 (0.1 mg/kg, i.p.) induced a profound antidepressant effect in the tail suspension test (TST) and in the forced swim test (FST) in mice. This drug combination did not impair memory, as measured using the Morris water maze (MWM), and did not influence the locomotor activity of mice. Furthermore, we found that an AMPA receptor antagonist, NBQX (10 mg/kg), completely reversed the antidepressant-like activity of a mixture of scopolamine and LY341495 in the TST. However, this effect was not influenced by para-chlorophenylalanine (PCPA) pre-treatment, indicating a lack of involvement of serotonergic system activation in the antidepressant-like effects of jointly given scopolamine and LY341495. Therefore, the combined administration of low doses of the antimuscarinic drug scopolamine and the group II mGlu receptor antagonist LY341495 might be a new, effective and safe strategy in the therapy of depression.
authors: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors: Karolina
authors: K
authors: Podkowa
authors: Faculty of Pharmacy, Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St, 30-688 Krakow, Poland.
authors: Adrian
authors: A
authors: Podkowa
authors: Faculty of Pharmacy, Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St, 30-688 Krakow, Poland.
authors: Kinga
authors: K
authors: Sałat
authors: Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Krakow, Poland.
authors: Tomasz
authors: T
authors: Lenda
authors: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors: Andrzej
authors: A
authors: Pilc
authors: Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland. Electronic address: nfpaluch@cyf-kr.edu.pl.
authors: Agnieszka
authors: A
authors: Pałucha-Poniewiera
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D003866:Depressive Disorder / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011810:Quinoxalines / Q000008:administration & dosage; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012601:Scopolamine / Q000008:administration & dosage*; D012701:Serotonin / Q000378:metabolism; D014966:Xanthenes / Q000008:administration & dosage*
chemical_list: D000596:Amino Acids; D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D011810:Quinoxalines; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012701:Serotonin; D012601:Scopolamine
keywords: Antidepressant; Depression; Forced swim test; LY341495; Morris water maze; Scopolamine; Tail suspension test