Additive Interaction Between Scopolamine and Nitric Oxide Agents on Immobility in the Forced Swim Test But Not Exploratory Activity in the Hole-Board Publisher Pubmed



Nasehi M¹ ; Mohammadimahdiabadihasani MH² ; Ebrahimighiri M³ ; Zarrindast MR^{2, 4, 5, 6}
Source: Psychopharmacology Published:2019

Abstract

Rationale: The muscarinic cholinergic antagonist scopolamine has received an attention due to its unique antidepressant effects. However, the considerable adverse effects on nervous system limit the use of scopolamine as a psychiatric drug. Objective: In order to overcome the limitations and increase the therapeutic effects of scopolamine, we decided to examine the effects of joint administration of sub-effective dose of scopolamine and the sub-effective dose of a nitric oxide (NO) precursor l-Arginine or a non-selective nitric oxide synthase (NOS) inhibitor l-NAME on depression- and anxiety-related behaviors in male NMRI mice. Methods: To this aim, animal behavior was assessed in the forced swim test (FST) and hole-board apparatus. Results: Scopolamine (0.05 mg/kg) significantly decreased immobility time in the FST, suggesting an antidepressant-like effect. Moreover, l-Arginine (50 mg/kg) produced an antidepressant-like response in the FST and decreased head-dip counts in the hole-board apparatus, indicating an anxiety-like effect. The same doses of scopolamine and l-Arginine decreased the locomotor activity in mice. Joint administration of sub-effective dose of scopolamine (0.01 mg/kg) with a low dose of l-Arginine (25 mg/kg) or l-NAME (1 mg/kg) induced a profound antidepressant-like effect in the FST. These drug combinations did not influence on anxiety-related behaviors. Meanwhile, l-NAME alone did not alter the performance of mice in the FST and hole-board. Isobolographic analysis revealed an additive effect for scopolamine and l-Arginine or l-NAME. Conclusion: Data suggests that NO agents could positively impact the therapeutic profile of scopolamine, because they might be useful for inducing antidepressant-like effect associated to scopolamine. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.