Better antidepressant efficacy of mecamylamine in combination with L-NAME than with L-arginine

Ebrahimi-Ghiri, Mohaddeseh; Mohammadi-Mahdiabadi-Hasani, Mohammad-Hossein; Nasehi, Mohammad; Zarrindast, Mohammad‐Reza

doi:10.1016/j.bbr.2020.112604

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…Here, we showed that nNOS expression was up-regulated in the hippocampus by LPS. Similar to mecamylamine, the expression of nNOS was normalized by a single dose of MH 1 day later . We also found MH’s antidepressant-like effects were blunted by l -arginine (NO precursor), which was similar to Atorvastatin .…”

Section: Discussionsupporting

confidence: 55%

“…Similar to mecamylamine, the expression of nNOS was normalized by a single dose of MH 1 day later. 27 We also found MH's antidepressant-like effects were blunted by Larginine (NO precursor), which was similar to Atorvastatin. 28 It was agreed that increasing the level of NO by drug pretreatment reduced the antidepressant response of MH, and drugs inhibiting the production of the NO signal induced a subeffective dose of MH to produce antidepressant effects.…”

Section: ■ Discussionmentioning

confidence: 99%

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Antidepressant-like Effect of Merazin Hydrate Depends on NO/ERK by Suppressing Its Downstream NF-κB or Nonactivating CREB/BDNF in Mouse Hippocampus

Liu

Huang

et al. 2020

ACS Chem. Neurosci.

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Merazin hydrate (MH), an essential ingredient of Fructus aurantii, has been identified to have an antidepressant-like effect. However, the molecular mechanisms of MH modulate depressive behavior are largely uncharacterized. Here, in lipopolysaccharide-induced mice, we identified that a single administration of MH recovered depressive behaviors and down-regulated the expressions of neuronal nitric oxide synthase (nNOS) in the hippocampus after 1 day. Activation of nNOS by l-arginine led to depressive behaviors, and inhibition of nNOS contributed to antidepressive behaviors. Notably, MH only reversed the expression of nNOS’s downstream NF-κB and not the CREB/BDNF pathway in the hippocampus, and MH’s antidepressant-like effects were prevented by Asatone (an agonist of NF-κB) and not H89 (an antagonist of CREB). MH also normalized the expressions of GFAP and IB-1 in dentate gyrus in the hippocampus and inflammatory factors such as IL-1β, IL-10, and TNF-α in serum. Overall, our studies reveal the molecular mechanisms of MH’s antidepressant-like effect.

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Section: Discussionsupporting

confidence: 55%

Section: ■ Discussionmentioning

confidence: 99%

Antidepressant-like Effect of Merazin Hydrate Depends on NO/ERK by Suppressing Its Downstream NF-κB or Nonactivating CREB/BDNF in Mouse Hippocampus

Liu

Huang

et al. 2020

ACS Chem. Neurosci.

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“…A hole-board test was conducted to evaluate locomotion and exploratory behavior of the mice (Nasehi et al 2019;Ebrahimi-Ghiri et al 2020b). Brie y, the testing apparatus was conducted using an opaque white acrylic board with 16 spaced holes located at equal distances from one another (3 cm diameter).…”

Section: Hole-board Testmentioning

confidence: 99%

Isobolographic analysis of the antidepressant interaction in two-drug combinations of citalopram, bupropion, and scopolamine in mice

Mohammadi-Mahdiabadi-Hasani

Ebrahimi-Ghiri

Khakpai

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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Depression and anxiety are psychiatric diseases that commonly occur together, and the patient burden and complexity increase when both are present. Comorbid anxiety and depression are often more resistant to common drug treatments such as antidepressants. Combination therapy is a suggested approach in treating these patients, where a decline of doses could reduce undesirable outcomes and still achieve optimal effects. We, therefore, conducted a preclinical study to assess the effect of two-drug combinations of citalopram, bupropion, and scopolamine on anxiety-and antidepressive-like behaviors in male NMRI mice and aimed to determine the nature of the interaction between components. Anxiety-or antidepressive-like activity of mice was assessed by the hole-board or forced swim test (FST), respectively. Our results revealed that citalopram (0.01-0.25 mg/kg; i.p.), bupropion (1-9 mg/kg; i.p.) or scopolamine (0.01-0.1 mg/kg; i.p.) diminished immobility time in the FST, suggesting an antidepressivelike effect. Citalopram decreased dead-dip counts in the hole-board, indicating an anxiogenic-like activity.All two-drug combinations, at inactive doses, exerted an antidepressive-like behavior. Only bupropion/scopolamine combination increased head-dip counts compared to the bupropion/saline group. Isobolographic analysis revealed an antidepressive synergy effect between citalopram plus bupropion, and an antidepressive additive impact between scopolamine plus citalopram or bupropion. It should be noted that the higher dose of each drug alone declined locomotor activity, while two-drug combinations did not affect this parameter. These results suggest a stronger antidepressive effect for citalopram/bupropion combination than other two-drug combinations.

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Isobolographic Analysis of The Antidepressant Interaction in Two-Drug Combinations of Citalopram, Bupropion and Scopolamine in Mice

Mohammadi-Mahdiabadi-Hasani

Ebrahimi-Ghiri

Khakpai

et al. 2022

Preprint

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Depression and anxiety are psychiatric diseases that commonly occur together, and the patient burden and complexity increase when both are present. Comorbid anxiety and depression are often more resistant to common drug treatments such as antidepressants. Combination therapy is a suggested approach in treating these patients, where a decline of doses could reduce undesirable outcomes and still achieve optimal effects. We, therefore, conducted a preclinical study to assess the effect of two-drug combinations of citalopram, bupropion, and scopolamine on anxiety- and antidepressive-like behaviors in male NMRI mice and aimed to determine the nature of the interaction between components. Anxiety- or antidepressive-like activity of mice was assessed by the hole-board or forced swim test (FST), respectively. Our results revealed that citalopram (0.01- 0.25 mg/kg; i.p.), bupropion (1-9 mg/kg; i.p.) or scopolamine (0.01-0.1 mg/kg; i.p.) diminished immobility time in the FST, suggesting an antidepressive-like effect. Citalopram decreased dead-dip counts in the hole-board, indicating an anxiogenic-like activity. All two-drug combinations, at inactive doses, exerted an antidepressive-like behavior. Only bupropion/scopolamine combination increased head-dip counts compared to the bupropion/saline group. Isobolographic analysis revealed an antidepressive synergy effect between citalopram plus bupropion, and an antidepressive additive impact between scopolamine plus citalopram or bupropion. It should be noted that the higher dose of each drug alone declined locomotor activity, while two-drug combinations did not affect this parameter. These results suggest a stronger antidepressive effect for citalopram/bupropion combination than other two-drug combinations.

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Better antidepressant efficacy of mecamylamine in combination with L-NAME than with L-arginine

Cited by 3 publications

References 43 publications

Antidepressant-like Effect of Merazin Hydrate Depends on NO/ERK by Suppressing Its Downstream NF-κB or Nonactivating CREB/BDNF in Mouse Hippocampus

Antidepressant-like Effect of Merazin Hydrate Depends on NO/ERK by Suppressing Its Downstream NF-κB or Nonactivating CREB/BDNF in Mouse Hippocampus

Isobolographic analysis of the antidepressant interaction in two-drug combinations of citalopram, bupropion, and scopolamine in mice

Isobolographic Analysis of The Antidepressant Interaction in Two-Drug Combinations of Citalopram, Bupropion and Scopolamine in Mice

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